Abstract
Understanding the urine excretion profile for Δ9-tetrahydrocannabinol (THC) metabolites is important for accurate detection and interpretation of toxicological testing for cannabis use. Prior literature has primarily evaluated the urinary pharmacokinetics of the non-psychoactive THC metabolite 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) following smoked cannabis administration. The present study examined the urine THCCOOH excretion profile following oral cannabis administration in 18 healthy adults. Following ingestion of a cannabis-containing brownie with 10, 25 or 50 mg of THC (N = 6 per dose), urine specimens were collected on a closed residential research unit for 6 days, followed by three outpatient visits on Days 7–9. Average maximum concentrations (Cmax) of THCCOOH were 107, 335 and 713 ng/mL, and average times to maximum concentration (Tmax) were 8, 6 and 9 h for the 10, 25 and 50 mg THC doses, respectively. Detection windows to first positive and last positive varied as a function of dose; higher doses had shorter time to first positive and longer time to last positive. Considerable inter-subject variability was observed on study outcomes. Gas chromatography/mass spectrometry (GC/MS; 15 ng/mL cutoff) was used as the criterion to assess sensitivity, specificity and agreement for THCCOOH qualitative immunoassay tests using 20, 50 and 100 ng/mL cutoffs. The 50 ng/mL cutoff displayed good sensitivity (92.5%), specificity (92.4%) and overall agreement (92.4%), whereas the 20 ng/mL cutoff demonstrated poor specificity (58.4%), and the 100 ng/mL cutoff exhibited reduced sensitivity (70.9%). Ingestion of cannabis brownies containing the 10 and 25 mg THC doses yielded THCCOOH concentrations that differed in magnitude and time course from those previously reported for the smoked route of administration of comparable doses.
Introduction
The national and international regulation of cannabis is changing. As of October 2017, 29 US states and the District of Columbia (DC) passed legislation that approved medicinal use of cannabis, and non-medicinal (“recreational”) use of cannabis has been legalized in eight states and DC. In 2015, an estimated 22 million Americans were current (past month) cannabis users (1), and in 2016, ~1.25 million were state-registered medicinal cannabis users (2). In parallel with the increase in use and availability of cannabis, the perceived risks and stigma associated with cannabis have decreased (3–5).
The introduction of retail cannabis dispensaries in states where cannabis use has been legalized has resulted in a proliferation of novel cannabis product types, and now affords consumers an extensive variety of options. Beyond traditional smoke-able preparations (e.g., joints, pipes, bongs), new retail products include “edibles” (e.g., brownies, cookies, gummies), beverages, concentrated extracts (e.g., wax, shatter), tinctures, transdermal products and suppositories. Variations in the route of administration and vehicle of drug delivery may impact the time course and magnitude of drug effects, including the absorption and disposition of the drug in biological fluids.
Currently, urine drug testing remains the primary forensic method for detecting cannabis use. Accurate detection of recent cannabis use is of growing significance and has important implications for workplace drug use and drug testing policies (6, 7), forensic investigations (8–10), and outpatient substance abuse treatment and research (11–13). Smoking is the most common route of administration for cannabis, and most research on cannabinoid detection in urine has evaluated smoked cannabis. Oral administration of cannabis has become increasingly popular, and, compared with the smoked route of administration, has a later time to onset and longer duration of pharmacodynamic drug effects (14, 15).
Numerous studies have examined the disposition of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) in humans following ingestion of products containing Δ9-tetrahydrocannabinol, the primary psychoactive component of the cannabis plant. For example, prior work has assessed the urinary disposition of THCCOOH after study participants ingested cannabis resin (16), cannabis seed oil (17), hemp oil (18, 19) or synthetic THC (20). Urinary THC metabolites were detectable during short- and long-term sample collection periods among individuals with and without a history of cannabis use. However, only three studies have evaluated the disposition of THCCOOH in humans following oral ingestion of raw cannabis or cannabis resin (16, 21, 22). Those studies determined that there were dose-related differences in the disposition of THCCOOH in urine and suggested that there may be differences in the concentration and time course of detection compared with the smoked route of cannabis self-administration. However, those studies were conducted with small sample sizes (3–5 participants), some included volunteers that were current cannabis users at the time of study participation, participants were exclusively male, and one study was limited to a 72-h sample collection window and was less controlled, such that participants could leave the study site and return for scheduled urine collection times. The current study aimed to extend research on the disposition of THCCOOH in urine following a single administration of oral cannabis to healthy adults with a history of cannabis use, but no recent use or detectable urine cannabinoids at baseline. Current drug test methods were utilized and the sensitivity, specificity and agreement between immunoassay (IA) tests at three different cutoffs were evaluated with reference to gas chromatography–mass spectrometry (GC/MS) test results.
Experimental methods
Participants
Eighteen healthy volunteers were recruited from the greater Baltimore area by media advertisements and word-of-mouth. Participants were eligible for screening if they were between 18 and 45 years of age, had a history of cannabis exposure, but had not used cannabis or other illicit substances in the 3 months prior to the screening date. Volunteers were deemed healthy and eligible to participate in the study through a battery of assessments including medical history, an electrocardiogram (EKG), and routine blood chemistry, hematology and serology analysis.
Study design and experimental procedures
Study volunteers completed a brief telephone interview and a laboratory assessment to determine study eligibility. Written informed consent was obtained at the laboratory screening assessment. The study was approved by the Johns Hopkins Medicine Institutional Review Board (IRB) and was conducted in accordance with ethical standards outlined in the Declaration of Helsinki. Participants received compensation for their time.
The screening process included a self-report questionnaire collecting demographic information, medical history and history of licit and illicit substance use, including a Timeline Follow Back (23) assessment, where participants reported substance use for each day over the previous 90 days. Substances reported on this assessment included tobacco cigarettes, alcohol, all forms of medicine, and all illicit drugs. In addition to self-report assessments, participants underwent a physical examination that assessed major organ systems, musculoskeletal system, general appearance and an electrocardiogram (EKG) to determine cardiovascular health. Blood, urine and breath specimens were taken for routine clinical chemistry, hematology, serology, testing for alcohol and illicit drug use, and serum pregnancy (females only).
The study used a randomized, double-blind, between-subjects design that tested three doses of cannabis. A single batch of cannabis obtained from the National Institute on Drug Abuse (NIDA) Drug Supply Program containing ~11% total THC, 0.1% cannabidiol (CBD) and 0.8% cannabinol (CBN) was used to prepare brownies containing 10, 25, and 50 mg doses of THC. Preparation of the cannabis-containing brownies was completed at the Johns Hopkins Behavioral Pharmacology Research Unit (BPRU) Pharmacy. Specifically, individually weighed doses of cannabis were ground into a powder using a food processor, and then heated at 250 °F (130°C) for 30 min in order to catalyze decarboxylation of tetrahydrocannabinolic acid (THC-A) to THC. The decarboxylated cannabis was then mixed into brownie batter; each dose was prepared in a separate individual baking tray to ensure exact dosing. Testing of product samples at each target dose confirmed the conversion of THC-A to THC and that target doses were reliably achieved. The brownies were prepared 24–48 h prior to administration.
Six participants (three males and three females) were assigned to each experimental dose. Data were collected over nine consecutive days: 6 days in a closed residential research unit and single outpatient visits were then conducted on the following three consecutive days. Participants arrived to the BPRU around 07:30 h on the first day of the study. Urine samples were collected to screen for recent drug use and pregnancy (women only), and breath alcohol testing was performed; participation in the study was contingent on negative results for all tests. One current tobacco user was provided with a 14 mg nicotine patch for use only during the residential study period and caffeine drinkers were permitted to consume one caffeinated beverage each day.
Participants ate a standard low-fat breakfast of toast and jelly, and were not permitted to eat again until 30 min following ingestion of the study drug. After all baseline assessments were completed, participants consumed a single cannabis-containing brownie in its entirety under direct staff observation within 5 min. All urine voids from each participant were collected over the 6-day residential study period, and single spot voids were collected during the three outpatient follow-up visits. Whole blood, oral fluid, pharmacodynamic measures of subjective drug effects, cardiovascular effects and cognitive performance evaluations were also conducted. Results of those assessments have been previously published (15).
Urine collection and testing procedures
Spot specimen collection occurred at Baseline and 1, 2, 3 and 4 h after oral cannabis dosing was completed. Subsequent to the collection at Hour 4, urine voids were pooled during the following time periods: 4–6, 6–8, 8–12, 12–22, 22–26, 26–30, 30–34, 34–46, 46–50, 50–54, 54–58, 58–70, 70–74, 74–78, 78–82, 82–94, 94–98, 98–102, 102–106, 106–118, 118–122, 122–126 and 126–130 h after ingestion of the study drug. Participants were asked to attempt to void at the end of each designated time period. Spot urine specimens were also collected during outpatient visits on Days 7, 8 and 9. For each time point sample, two 30 mL aliquots of urine (Bottles A and B) were transferred into polypropylene bottles, which were wrapped with parafilm and stored in a −10°F freezer. At the end of the study, all samples were shipped overnight to Clinical Reference Laboratory (CRL; Lenexa, KS, USA) on dry ice to ensure the integrity of the specimens.
Analytical methods
Analyses of urine specimens were conducted by Clinical Reference Laboratory (CRL), Lenexa, KS. Bottle A specimens were thawed and aliquots were analyzed by immunoassay and gas chromatography–mass spectrometry (GC/MS) as previously described (24).
Initial analyses of specimens by immunoassays were conducted according to manufacturer’s procedure with the Microgenics DRI assay on a Bayer ADVAI 2400 analyzer for cannabinoids in urine at 20, 50 and 100 ng/mL cutoff concentrations. Creatinine was determined with Siemens modified Jaffe reagent. Specific gravity was determined with a Rudolph J57 refractometer. Determinations of pH were made with Axiom pH reagents (Axiom Diagnostics, Tampa, FL).
The GC/MS method had a limit of quantification (LOQ) for THCCOOH of 0.75 ng/mL and an upper limit of linearity of (ULOL) of 600 ng/mL. Specimens with concentrations ≥ ULOL were diluted to provide accurate quantitation. Criteria for acceptance of results included the following: retention times of analyte and internal standard within ±2% of the calibrator; ion ratios within ±20% of the calibrator; and positive control concentrations ±20% of established concentrations.
Data presentation and analysis
Participant demographics and results of urine specimens are presented using descriptive statistics. Agreement between results of the immunoassay (IA) and GC/MS confirmation testing was conducted for urine THCCOOH test results. As in our prior work (24), sensitivity, specificity and agreement calculations were based on comparison of IA results at three separate cutoffs (20, 50 and 100 ng/mL, respectively) relative to a confirmatory GC/MS cutoff of 15 ng/mL. The 15 ng/mL GC/MS cutoff corresponds to the value adhered to by the Substance Abuse and Mental Health Services Administration’s (SAMHSA) Mandatory Guidelines for Federal Workplace Drug Testing programs (25). The calculation of sensitivity, specificity and agreement were based on the following: (1) true positive (TP; IA response ≥ cutoff concentration and GC/MS positive, ≥15 ng/mL), (2) true negative (TN; IA response < cutoff concentration and GC/MS negative, <15 ng/mL), (3) false positive (FP; IA response ≥ cutoff concentration and GC/MS negative), or (4) false negative (FN; IA response < cutoff concentration and GC/MS positive). Sensitivity, specificity and agreement were calculated as follows: sensitivity = (100 × [TP/(TP + FN)]); specificity = (100 × [(TN/(TN + FP))]); agreement = (100 × [(TP + TN)/(TP + TN + FP + FN)]).
Results
Participants
Participant demographics and select substance use characteristics are presented in Table I. Participants were predominantly Caucasian, tobacco non-smokers, who reported a mean of six alcoholic drinks per week, and 2 years since last using cannabis. With the exception of birth control, participants denied use of prescription and over-the-counter medications for at least 2 weeks prior to dosing.
Table I.
Participant characteristics (N = 18).
| Sex (% female) | 50 |
| Race (% Caucasian) | 78 |
| Age (years) | 26.1 (3.9) |
| Weight (kg) | 71.3 (16.9) |
| Height (cm) | 173.9 (10.7) |
| Body mass index | 23.3 (3.3) |
| Time since last cannabis use (months) | 24.2 (31.4) |
| Tobacco cigarette smokers at intake (#) | 1 |
| Alcohol drinks/week (past 30 days) | 5.7 (5.5) |
Values are means and standard deviations (SD), except where otherwise noted.
GC/MS results
Complete quantitative and qualitative test results for each participant are presented in Table II, and mean THCCOOH urine specimen concentrations following cannabis ingestion are displayed in Figure 1 as a function of dose. Mean Cmax THCCOOH concentrations increased in a linear fashion as a function of dose (Table III). Ingestion of the 10 mg THC dose produced the lowest Cmax value (mean = 106.8 ng/mL; range = 33.8–277.9 ng/mL) and the 50 mg THC dose resulted in the highest concentration of THCCOOH (mean = 712.55 ng/mL; range = 215.5–1024.8 ng/mL). Compared to the lowest dose (10 mg THC), Cmax values for the 25 and 50 mg THC doses were more variable. Mean times corresponding to maximum THCCOOH concentrations (Tmax) are displayed in Table III, and were 8.2 h, 5.8 h and 9.2 h after ingestion of the study drug was completed for the 10, 25 and 50 mg THC doses, respectively. Considerable between-subject variability in Tmax values was also apparent. In contrast to the 25 mg THC dose (minimum = 4 h, maximum = 7 h), the 10 (minimum = 4 h, maximum = 17 h) and 50 mg THC doses (minimum = 3 h, maximum = 17 h) were widely distributed. There were no systematic differences between males and females at any dose.
Table II.
Analyses of urine specimens following oral consumption of cannabis brownies.
| Participant number | Time (h) | THC dose (mg) | THCCOOH GC/MS (ng/mL) | Volume of specimen | Creatinine (mg/dL) | Specific gravity | pH | 20 ng/mL IA THCCOOH (equivalent IA response = 20) | 50 ng/mL IA THCCOOH (equivalent IA response = 50) | 100 ng/mL IA THCCOOH (equivalent IA response = 100) |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 M | BL | 10 | 0.0 | 110 | 174.2 | 1.0280 | 6.1 | −17 | −7 | −7 |
| 1 M | 1 | 10 | 0.0 | 46 | 205.6 | 1.0295 | 6.3 | −3 | −3 | −2 |
| 1 M | 2 | 10 | 9.6 | 47 | 165.5 | 1.0271 | 5.8 | 81 | 95 | 136 |
| 1 M | 3 | 10 | 44.6 | 46 | 169.9 | 1.0269 | 5.8 | 83 | 99 | 136 |
| 1 M | 4 | 10 | 77.2 | 50 | 169.6 | 1.0275 | 6.0 | 82 | 99 | 140 |
| 1 M | 4–6 | 10 | 67.4 | 105 | 162.3 | 1.0274 | 6.2 | 79 | 98 | 140 |
| 1 M | 6–8 | 10 | 51.6 | 81 | 187.3 | 1.0287 | 6.1 | 75 | 96 | 138 |
| 1 M | 8–10 | 10 | 40.4 | 80 | 204.8 | 1.0292 | 6.1 | 76 | 95 | 135 |
| 1 M | 10–12 | 10 | 64.8 | 50 | 191.8 | 1.0290 | 6.4 | 79 | 98 | 136 |
| 1 M | 12–22 | 10 | 63.0 | 90 | 279.6 | 1.0310 | 6.2 | 75 | 97 | 135 |
| 1 M | 22–26 | 10 | 51.0 | 120 | 229.6 | 1.0256 | 7.3 | 87 | 104 | 139 |
| 1 M | 26–30 | 10 | 13.8 | 460 | 66.1 | 1.0123 | 7.5 | 99 | 55 | 45 |
| 1 M | 30–34 | 10 | 19.4 | 270 | 127.3 | 1.0219 | 6.6 | 88 | 97 | 92 |
| 1 M | 34–46 | 10 | 20.4 | 200 | 193.2 | 1.0269 | 6.2 | 78 | 95 | 102 |
| 1 M | 46–50 | 10 | 15.3 | 350 | 225.1 | 1.0243 | 6.7 | 85 | 89 | 82 |
| 1 M | 50–54 | 10 | 8.9 | 410 | 94.0 | 1.0164 | 7.6 | 69 | 26 | 22 |
| 1 M | 54–58 | 10 | 5.2 | 350 | 107.5 | 1.0184 | 7.2 | 55 | 19 | 14 |
| 1 M | 58–70 | 10 | 7.6 | 650 | 131.8 | 1.0196 | 6.7 | 68 | 23 | 17 |
| 1 M | 70–74 | 10 | 5.1 | 260 | 140.1 | 1.0163 | 6.2 | 63 | 18 | 16 |
| 1 M | 74–78 | 10 | 1.7 | 810 | 38.9 | 1.0066 | 7.2 | 13 | 4 | 3 |
| 1 M | 78–82 | 10 | 3.9 | 370 | 84.9 | 1.0135 | 5.7 | 26 | 7 | 7 |
| 1 M | 82–94 | 10 | 2.3 | 400 | 99.8 | 1.0127 | 6.0 | 17 | 5 | 4 |
| 1 M | 94–98 | 10 | 5.5 | 160 | 211.9 | 1.0230 | 7.5 | 35 | 12 | 7 |
| 1 M | 98–102 | 10 | 2.8 | 360 | 100.3 | 1.0176 | 7.6 | 7 | 3 | 0 |
| 1 M | 102–106 | 10 | 0.0 | 720 | 28.1 | 1.0053 | 7.4 | 3 | 0 | −1 |
| 1 M | 106–118 | 10 | 2.5 | 450 | 215 | 1.0232 | 6.3 | 14 | 2 | 1 |
| 1 M | 118–122 | 10 | 2.9 | 120 | 204.8 | 1.0217 | 7.6 | 9 | 3 | 2 |
| 1 M | 122–126 | 10 | 1.1 | 610 | 74.3 | 1.0134 | 7.6 | 2 | 0 | 0 |
| 1 M | 126–130 | 10 | 1.6 | 550 | 63.0 | 1.0112 | 6.9 | 1 | −2 | −1 |
| 1 M | Day 7 | 10 | 1.6 | NM | 167.8 | 1.0211 | 7.9 | −3 | −1 | −2 |
| 6 F | BL | 10 | 0.0 | 260 | 23.6 | 1.0038 | 6.7 | 2 | 1 | 0 |
| 6 F | 1 | 10 | 0.0 | 785 | 8.3 | 1.0015 | 6.7 | 9 | 4 | 2 |
| 6 F | 2 | 10 | 4.4 | 530 | 11.5 | 1.0020 | 7.0 | 99 | 41 | 34 |
| 6 F | 3 | 10 | 24.0 | 280 | 25.6 | 1.0046 | 7.6 | 109 | 100 | 109 |
| 6 F | 4 | 10 | 53.4 | 170 | 37.0 | 1.0066 | 7.6 | 108 | 106 | 137 |
| 6 F | 4–6 | 10 | 277.9 | 87 | 134.4 | 1.0182 | 6.9 | 90 | 101 | 142 |
| 6 F | 6–8 | 10 | 100.6 | 115 | 66.4 | 1.0101 | 5.8 | 98 | 106 | 141 |
| 6 F | 8–10 | 10 | 60.0 | 110 | 72.1 | 1.0103 | 5.8 | 100 | 104 | 146 |
| 6 F | 10–12 | 10 | 77.0 | 400 | 93.2 | 1.0130 | 6.4 | 100 | 105 | 142 |
| 6 F | 12–22 | 10 | 102.6 | 260 | 195.9 | 1.0197 | 5.4 | 92 | 100 | 138 |
| 6 F | 22–26 | 10 | 22.7 | 460 | 48.4 | 1.0061 | 6.1 | 104 | 90 | 78 |
| 6 F | 26–30 | 10 | 21.2 | 410 | 56.8 | 1.0071 | 6.0 | 108 | 92 | 80 |
| 6 F | 30–34 | 10 | 14.8 | 600 | 39.0 | 1.0065 | 7.5 | 104 | 45 | 36 |
| 6 F | 34–46 | 10 | 31.5 | 720 | 93.9 | 1.0122 | 7.2 | 99 | 89 | 78 |
| 6 F | 46–50 | 10 | 41.8 | 110 | 171.6 | 1.0145 | 5.7 | 100 | 102 | 123 |
| 6 F | 50–54 | 10 | 9.8 | 460 | 33.5 | 1.0049 | 7.4 | 62 | 20 | 17 |
| 6 F | 54–58 | 10 | 6.2 | 750 | 34.1 | 1.0057 | 7.2 | 57 | 18 | 15 |
| 6 F | 58–70 | 10 | 17.6 | 650 | 113.6 | 1.0133 | 7.0 | 97 | 57 | 43 |
| 6 F | 70–74 | 10 | 16.0 | 280 | 76.5 | 1.0088 | 6.4 | 101 | 48 | 37 |
| 6 F | 74–78 | 10 | 10.1 | 660 | 44.9 | 1.0082 | 7.5 | 54 | 19 | 15 |
| 6 F | 78–82 | 10 | 5.9 | 750 | 35.7 | 1.0069 | 7.2 | 30 | 9 | 9 |
| 6 F | 82–94 | 10 | 12.7 | 660 | 96.3 | 1.0124 | 6.8 | 78 | 28 | 21 |
| 6 F | 94–98 | 10 | 9.6 | 1310 | 115.2 | 1.0128 | 5.6 | 75 | 26 | 23 |
| 6 F | 98–102 | 10 | 2.1 | 750 | 19.1 | 1.0030 | 7.3 | 14 | 6 | 5 |
| 6 F | 102–106 | 10 | 3.5 | 600 | 39.7 | 1.0066 | 7.2 | 18 | 5 | 4 |
| 6 F | 106–118 | 10 | 4.2 | 1135 | 56.8 | 1.0080 | 7.0 | 22 | 7 | 5 |
| 6 F | 118–122 | 10 | 6.1 | 150 | 161.0 | 1.0166 | 5.7 | 39 | 13 | 10 |
| 6 F | 122–126 | 10 | 1.8 | 625 | 43.8 | 1.0060 | 6.6 | 11 | 4 | 4 |
| 6 F | 126–130 | 10 | 0.0 | 410 | 26.2 | 1.0036 | 6.1 | 6 | 2 | 0 |
| 6 F | Day 7 | 10 | 2.2 | NM | 268.1 | 1.0236 | 5.6 | 7 | 0 | 1 |
| 6 F | Day 8 | 10 | 1.9 | NM | 217.6 | 1.0249 | 5.3 | −4 | −3 | −4 |
| 6 F | Day 9 | 10 | 3.0 | NM | 321.7 | 1.2690 | 5.5 | 7 | 1 | 4 |
| 12 F | BL | 10 | 0.0 | 180 | 24.4 | 1.0041 | 6.4 | 10 | 3 | 3 |
| 12 F | 1 | 10 | 0.0 | 200 | 36.1 | 1.0061 | 6.3 | 2 | −1 | 0 |
| 12 F | 2 | 10 | 5.3 | 190 | 31.1 | 1.0064 | 7.1 | 96 | 84 | 68 |
| 12 F | 3 | 10 | 5.2 | 580 | 8.2 | 1.0019 | 7.1 | 96 | 45 | 35 |
| 12 F | 4 | 10 | 10.5 | 610 | 9.1 | 1.0019 | 6.8 | 99 | 58 | 42 |
| 12 F | 4–6 | 10 | 19.2 | 860 | 14.5 | 1.0025 | 7.2 | 104 | 66 | 48 |
| 12 F | 6–8 | 10 | 14.4 | 750 | 13.7 | 1.0025 | 7.2 | 100 | 45 | 32 |
| 12 F | 8–10 | 10 | 22.6 | 530 | 21.1 | 1.0039 | 7.1 | 101 | 110 | 94 |
| 12 F | 10–12 | 10 | 37.7 | 360 | 29.8 | 1.0067 | 6.9 | 99 | 116 | 135 |
| 12 F | 12–22 | 10 | 57.9 | 700 | 52.7 | 1.0068 | 7.0 | 98 | 118 | 137 |
| 12 F | 22–26 | 10 | 25.5 | 560 | 24.1 | 1.0041 | 7.0 | 102 | 62 | 43 |
| 12 F | 26–30 | 10 | 13.9 | 960 | 20.8 | 1.0036 | 6.2 | 84 | 32 | 23 |
| 12 F | 30–34 | 10 | 14.7 | 700 | 25.9 | 1.0051 | 7.0 | 85 | 30 | 23 |
| 12 F | 34–46 | 10 | 17.5 | 1260 | 42.7 | 1.0063 | 6.9 | 90 | 35 | 28 |
| 12 F | 46–50 | 10 | 10.7 | 635 | 32.4 | 1.0049 | 7.2 | 50 | 20 | 14 |
| 12 F | 50–54 | 10 | 5.1 | 810 | 26.8 | 1.0052 | 6.6 | 20 | 9 | 7 |
| 12 F | 54–58 | 10 | 5.6 | 610 | 26.4 | 1.0056 | 6.8 | 19 | 7 | 7 |
| 12 F | 58–70 | 10 | 14.7 | 655 | 91.4 | 1.0138 | 7.1 | 57 | 19 | 14 |
| 12 F | 70–74 | 10 | 4.3 | 800 | 29.9 | 1.0071 | 7.0 | 14 | 5 | 4 |
| 12 F | 74–78 | 10 | 0.0 | 640 | 20.7 | 1.0051 | 6.9 | 8 | 2 | 3 |
| 12 F | 78–82 | 10 | 3.6 | 800 | 36.4 | 1.0076 | 7.3 | 10 | 3 | 4 |
| 12 F | 82–94 | 10 | 7.8 | 580 | 85.3 | 1.0122 | 6.4 | 22 | 8 | 8 |
| 12 F | 94–98 | 10 | 5.9 | 210 | 83.0 | 1.0132 | 7.1 | 15 | 6 | 5 |
| 15 M | BL | 10 | 0.0 | 100 | 145.8 | 1.0206 | 5.9 | −10 | −6 | −7 |
| 15 M | 1 | 10 | 0.0 | 580 | 20.3 | 1.0042 | 6.5 | 6 | 3 | 3 |
| 15 M | 2 | 10 | 5.5 | 250 | 39.1 | 1.0074 | 6.3 | 107 | 71 | 58 |
| 15 M | 3 | 10 | 10.8 | 350 | 32.0 | 1.0058 | 5.6 | 109 | 93 | 71 |
| 15 M | 4 | 10 | NS | 230 | NS | NS | NS | NS | NS | NS |
| 15 M | 4–6 | 10 | 31.3 | 290 | 76.1 | 1.0133 | 6.6 | 103 | 113 | 101 |
| 15 M | 6–8 | 10 | 33.8 | 230 | 102.6 | 1.0176 | 7.1 | 94 | 114 | 104 |
| 15 M | 8–10 | 10 | 27.6 | 150 | 125.6 | 1.0176 | 6.6 | 96 | 116 | 126 |
| 15 M | 10–12 | 10 | 9.5 | 650 | 54.8 | 1.0091 | 7.3 | 102 | 45 | 36 |
| 15 M | 12–22 | 10 | 20.7 | 1210 | 75.9 | 1.0096 | 7.1 | 106 | 108 | 87 |
| 15 M | 22–26 | 10 | 14.8 | 810 | 40.4 | 1.0056 | 7.1 | 109 | 50 | 36 |
| 15 M | 26–30 | 10 | 31.5 | 380 | 110.8 | 1.0148 | 6.6 | 98 | 111 | 99 |
| 15 M | 30–34 | 10 | 9.9 | 600 | 58.3 | 1.0067 | 6.7 | 96 | 34 | 28 |
| 15 M | 34–46 | 10 | 11.1 | 1650 | 78.4 | 1.0094 | 6.2 | 97 | 39 | 30 |
| 15 M | 46–50 | 10 | 12.9 | 360 | 94.5 | 1.0099 | 7.3 | 87 | 36 | 27 |
| 15 M | 50–54 | 10 | 6.0 | 885 | 49.7 | 1.0073 | 7.4 | 42 | 14 | 14 |
| 15 M | 54–58 | 10 | 5.1 | 560 | 53.1 | 1.0066 | 6.2 | 38 | 14 | 14 |
| 15 M | 58–70 | 10 | 5.3 | 1400 | 103.7 | 1.0104 | 6.6 | 43 | 16 | 12 |
| 15 M | 70–74 | 10 | 5.7 | 350 | 120.9 | 1.0114 | 6.7 | 44 | 16 | 13 |
| 15 M | 74–78 | 10 | 7.9 | 630 | 139.1 | 1.0148 | 6.5 | 49 | 15 | 15 |
| 15 M | 78–82 | 10 | 0.0 | 1035 | 38.1 | 1.0146 | 6.9 | 13 | 4 | 4 |
| 15 M | 82–94 | 10 | 3.0 | 2000 | 62.4 | 1.0062 | 6.6 | 15 | 6 | 4 |
| 15 M | 94–98 | 10 | NS | NS | NS | NS | NS | NS | NS | NS |
| 15 M | 98–102 | 10 | 3.9 | 610 | 142.5 | 1.0148 | 7.0 | 14 | 4 | 3 |
| 15 M | 102–106 | 10 | 0.0 | 850 | 57.3 | 1.0071 | 7.0 | 5 | 1 | 1 |
| 15 M | 106–118 | 10 | 0.0 | 1560 | 79.0 | 1.0067 | 6.4 | 7 | 1 | 1 |
| 15 M | 118–122 | 10 | 0.0 | 210 | 188.0 | 1.0161 | 7.3 | 7 | 0 | 1 |
| 15 M | 122–126 | 10 | 3.1 | 110 | 241.4 | 1.0208 | 7.3 | 8 | 2 | 2 |
| 20 M | BL | 10 | 0.0 | 225 | 77.7 | 1.0073 | 6.0 | −1 | −2 | −1 |
| 20 M | 1 | 10 | 0.0 | 300 | 45.5 | 1.0048 | 6.3 | 35 | 13 | 11 |
| 20 M | 2 | 10 | 12.2 | 350 | 22.4 | 1.0024 | 6.9 | 109 | 79 | 61 |
| 20 M | 3 | 10 | 14.0 | 215 | 52.1 | 1.0047 | 6.7 | 106 | 121 | 128 |
| 20 M | 4 | 10 | 21.4 | 430 | 29.3 | 1.0029 | 6.2 | 111 | 117 | 95 |
| 20 M | 4–6 | 10 | 52.1 | 420 | 59.7 | 1.0064 | 6.3 | 103 | 114 | 151 |
| 20 M | 6–8 | 10 | 32.6 | 385 | 46.0 | 1.0052 | 6.7 | 104 | 106 | 79 |
| 20 M | 8–10 | 10 | 53.2 | 325 | 81.4 | 1.0074 | 6.2 | 105 | 115 | 153 |
| 20 M | 10–12 | 10 | 116.5 | 100 | 175.1 | 1.0147 | 6.4 | 98 | 116 | 157 |
| 20 M | 12–22 | 10 | 78.2 | 860 | 125.7 | 1.0105 | 6.9 | 98 | 120 | 161 |
| 20 M | 22–26 | 10 | 60.3 | 210 | 142.4 | 1.0151 | 7.4 | 91 | 117 | 147 |
| 20 M | 26–30 | 10 | 25.6 | 510 | 85.5 | 1.0082 | 7.1 | 98 | 78 | 59 |
| 20 M | 30–34 | 10 | 32.6 | 360 | 132.3 | 1.0132 | 6.6 | 97 | 97 | 73 |
| 20 M | 34–46 | 10 | 16.4 | 1490 | 56.2 | 1.0062 | 7.1 | 89 | 35 | 26 |
| 20 M | 46–50 | 10 | 19.8 | 360 | 114.5 | 1.0099 | 6.6 | 94 | 45 | 38 |
| 20 M | 50–54 | 10 | 18.6 | 510 | 95.8 | 1.0092 | 7.0 | 92 | 34 | 25 |
| 20 M | 54–58 | 10 | 7.3 | 1175 | 48.8 | 1.0053 | 6.8 | 33 | 13 | 11 |
| 20 M | 58–70 | 10 | 7.3 | 1320 | 63.2 | 1.0068 | 7.1 | 27 | 11 | 9 |
| 20 M | 70–74 | 10 | NS | NS | NS | NS | NS | NS | NS | NS |
| 20 M | 74–78 | 10 | 12.2 | 290 | 145.4 | 1.0161 | 7.3 | 42 | 16 | 9 |
| 20 M | 78–82 | 10 | 5.1 | 725 | 74.5 | 1.0084 | 6.5 | 17 | 7 | 6 |
| 20 M | 82–94 | 10 | 0.0 | 1320 | 42.1 | 1.0051 | 6.8 | 7 | 3 | 2 |
| 20 M | 94–98 | 10 | 3.9 | 350 | 122.8 | 1.0133 | 6.7 | 9 | 2 | 2 |
| 20 M | 98–102 | 10 | 7.5 | 280 | 222.1 | 1.0217 | 7.2 | 16 | 4 | 5 |
| 20 M | 102–106 | 10 | 7.9 | 350 | 317.0 | 1.0257 | 6.2 | 11 | 2 | 2 |
| 20 M | 106–118 | 10 | 2.2 | 660 | 83.7 | 1.0069 | 5.6 | 7 | 0 | 0 |
| 20 M | 118–122 | 10 | 2.5 | 90 | 126.8 | 1.0151 | 7.6 | 3 | −2 | 0 |
| 20 M | 122–126 | 10 | 3.3 | 225 | 198.3 | 1.0179 | 7.7 | 4 | 1 | −2 |
| 22 F | BL | 10 | 0.0 | 105 | 60.3 | 1.0074 | 5.8 | 1 | 1 | 1 |
| 22 F | 1 | 10 | 0.0 | 500 | 7.9 | 1.0016 | 6.4 | −1 | −5 | −9 |
| 22 F | 2 | 10 | 0.0 | 280 | 18.8 | 1.0044 | 7.5 | 16 | 1 | −2 |
| 22 F | 3 | 10 | 9.8 | 150 | 27.9 | 1.0062 | 7.5 | 88 | 93 | 82 |
| 22 F | 4 | 10 | 14.5 | 200 | 18.6 | 1.0044 | 7.4 | 88 | 92 | 80 |
| 22 F | 4–6 | 10 | 77.5 | 100 | 93.4 | 1.0160 | 7.5 | 80 | 101 | 130 |
| 22 F | 6–8 | 10 | 67.1 | 100 | 110.1 | 1.0198 | 7.6 | 73 | 99 | 131 |
| 22 F | 8–10 | 10 | NS | NS | NS | NS | NS | NS | NS | NS |
| 22 F | 10–12 | 10 | 39.3 | 100 | 89.3 | 1.0178 | 7.6 | 78 | 101 | 129 |
| 22 F | 12–22 | 10 | 36.2 | 480 | 84.2 | 1.0130 | 7.3 | 82 | 99 | 131 |
| 22 F | 22–26 | 10 | 20.3 | 500 | 45.0 | 1.0086 | 7.4 | 84 | 89 | 74 |
| 22 F | 26–30 | 10 | 15.0 | 400 | 40.4 | 1.0093 | 7.5 | 85 | 63 | 42 |
| 22 F | 30–34 | 10 | 16.0 | 200 | 57.3 | 1.0138 | 7.4 | 79 | 76 | 53 |
| 22 F | 34–46 | 10 | 8.4 | 960 | 46.4 | 1.0073 | 7.0 | 81 | 33 | 21 |
| 22 F | 46–50 | 10 | 10.4 | 310 | 51.8 | 1.0078 | 7.6 | 78 | 31 | 19 |
| 22 F | 50–54 | 10 | 4.6 | 1110 | 21.0 | 1.0043 | 7.5 | 42 | 18 | 16 |
| 22 F | 54–58 | 10 | 8.2 | 390 | 39.8 | 1.0069 | 7.2 | 76 | 30 | 25 |
| 22 F | 58–70 | 10 | 5.9 | 1390 | 43.3 | 1.0075 | 7.5 | 43 | 19 | 15 |
| 22 F | 70–74 | 10 | 8.1 | 310 | 60.2 | 1.0080 | 7.5 | 71 | 28 | 23 |
| 22 F | 74–78 | 10 | 5.1 | 360 | 28.0 | 1.0054 | 7.1 | 35 | 17 | 11 |
| 22 F | 78–82 | 10 | 3.3 | 250 | 28.3 | 1.0053 | 6.5 | 26 | 13 | 12 |
| 22 F | 82–94 | 10 | 0.0 | 1620 | 35.1 | 1.0062 | 7.4 | 19 | 10 | 8 |
| 22 F | 94–98 | 10 | 4.0 | 320 | 62.1 | 1.0092 | 7.5 | 29 | 14 | 13 |
| 5 M | BL | 25 | 0.0 | 260 | 48.3 | 1.0080 | 7.1 | −1 | −2 | −2 |
| 5 M | 1 | 25 | 0.0 | 450 | 22.9 | 1.0038 | 6.8 | 44 | 15 | 11 |
| 5 M | 2 | 25 | 6.4 | 560 | 12.2 | 1.0020 | 7.2 | 109 | 64 | 52 |
| 5 M | 3 | 25 | 36.6 | 240 | 38.7 | 1.0055 | 7.5 | 104 | 107 | 141 |
| 5 M | 4 | 25 | 156.9 | 80 | 90.2 | 1.0112 | 6.8 | 104 | 105 | 143 |
| 5 M | 4–6 | 25 | 319.3 | 140 | 150.9 | 1.0177 | 6.9 | 94 | 102 | 141 |
| 5 M | 6–8 | 25 | 44.1 | 580 | 27.1 | 1.0047 | 7.0 | 110 | 109 | 126 |
| 5 M | 8–10 | 25 | 87.5 | 230 | 92.6 | 1.0134 | 6.6 | 96 | 107 | 142 |
| 5 M | 10–12 | 25 | 23.4 | 200 | 30.5 | 1.0049 | 6.2 | 109 | 101 | 99 |
| 5 M | 12–22 | 25 | 58.0 | 660 | 115 | 1.0135 | 6.0 | 100 | 105 | 144 |
| 5 M | 22–26 | 25 | 19.2 | 860 | 33.4 | 1.0052 | 6.7 | 110 | 84 | 68 |
| 5 M | 26–30 | 25 | 19.0 | 1100 | 22.8 | 1.0040 | 7.3 | 104 | 48 | 38 |
| 5 M | 30–34 | 25 | 28.8 | 730 | 56.6 | 1.0081 | 6.6 | 105 | 102 | 105 |
| 5 M | 34–46 | 25 | 19.2 | 1700 | 59.9 | 1.0076 | 7.1 | 107 | 85 | 68 |
| 5 M | 46–50 | 25 | 16.9 | 1460 | 56.5 | 1.0078 | 7.5 | 100 | 46 | 37 |
| 5 M | 50–54 | 25 | 12.1 | 460 | 44.5 | 1.0072 | 7.4 | 70 | 23 | 19 |
| 5 M | 54–58 | 25 | 9.1 | 840 | 67.2 | 1.0080 | 7.1 | 63 | 21 | 15 |
| 5 M | 58–70 | 25 | 7.1 | 1600 | 70.3 | 1.0087 | 7.5 | 35 | 12 | 8 |
| 5 M | 70–74 | 25 | 3.9 | 400 | 33.2 | 1.0062 | 7.4 | 17 | 6 | 3 |
| 5 M | 74–78 | 25 | 0.0 | 1000 | 26.6 | 1.0044 | 6.9 | 12 | 3 | 4 |
| 5 M | 78–82 | 25 | 4.8 | 1300 | 76.2 | 1.0089 | 6.9 | 23 | 8 | 6 |
| 5 M | 82–94 | 25 | 12.6 | 1230 | 41.0 | 1.0073 | 7.4 | 68 | 21 | 18 |
| 5 M | 94–98 | 25 | 5.9 | 310 | 110.1 | 1.0128 | 7.6 | 22 | 7 | 5 |
| 5 M | 98–102 | 25 | 0.0 | 480 | 48.9 | 1.0073 | 7.3 | 10 | 3 | 3 |
| 5 M | 102–106 | 25 | 0.0 | 900 | 44.1 | 1.0071 | 6.1 | 8 | 1 | 1 |
| 5 M | 106–118 | 25 | 3.3 | 1010 | 95.9 | 1.0122 | 6.4 | 9 | 2 | 1 |
| 8 F | BL | 25 | 0.0 | 390 | 27.6 | 1.0048 | 8.2 | 0 | −6 | −3 |
| 8 F | 1 | 25 | 0.0 | 200 | 20.1 | 1.0034 | 7.2 | 44 | 15 | 14 |
| 8 F | 2 | 25 | NS | NS | NS | NS | NS | NS | NS | NS |
| 8 F | 3 | 25 | 36.9 | 200 | 40.7 | 1.0068 | 7.5 | 100 | 118 | 148 |
| 8 F | 4 | 25 | 129.2 | 80 | 64.7 | 1.0085 | 7.0 | 100 | 116 | 150 |
| 8 F | 4–6 | 25 | 49.4 | 490 | 23.6 | 1.0033 | 7.0 | 110 | 121 | 155 |
| 8 F | 6–8 | 25 | 139.8 | 170 | 61.6 | 1.0084 | 6.8 | 99 | 116 | 149 |
| 8 F | 8–10 | 25 | 118.5 | 140 | 89 | 1.0113 | 6.1 | 99 | 117 | 156 |
| 8 F | 10–12 | 25 | 98.6 | 200 | 53.2 | 1.0095 | 6.5 | 102 | 114 | 154 |
| 8 F | 12–22 | 25 | 86.5 | 750 | 61.3 | 1.0080 | 6.2 | 101 | 117 | 154 |
| 8 F | 22–26 | 25 | 47.5 | 400 | 45.5 | 1.0081 | 7.4 | 99 | 115 | 146 |
| 8 F | 26–30 | 25 | 20.9 | 740 | 27.9 | 1.0039 | 6.9 | 102 | 106 | 94 |
| 8 F | 30–34 | 25 | 49.2 | 250 | 85.7 | 1.0095 | 6.5 | 101 | 115 | 149 |
| 8 F | 34–46 | 25 | 25.7 | 690 | 87.8 | 1.0087 | 6.3 | 102 | 113 | 103 |
| 8 F | 46–50 | 25 | 11.6 | 760 | 31.5 | 1.0051 | 7.4 | 91 | 35 | 27 |
| 8 F | 50–54 | 25 | 13.6 | 410 | 49.3 | 1.0081 | 7.2 | 100 | 47 | 36 |
| 8 F | 54–58 | 25 | 13.2 | 380 | 61.5 | 1.0078 | 6.8 | 102 | 48 | 35 |
| 8 F | 58–70 | 25 | 17.0 | 670 | 109 | 1.0115 | 6.6 | 9 | 59 | 42 |
| 8 F | 70–74 | 25 | 12.0 | 460 | 42.1 | 1.0069 | 7.5 | 65 | 24 | 18 |
| 8 F | 74–78 | 25 | 5.0 | 680 | 37.7 | 1.0067 | 7.4 | 31 | 12 | 9 |
| 8 F | 78–82 | 25 | 6.6 | 350 | 54.9 | 1.0086 | 7.3 | 33 | 11 | 8 |
| 8 F | 82–94 | 25 | 8.5 | 470 | 122.1 | 1.0123 | 6.0 | 55 | 19 | 12 |
| 8 F | 94–98 | 25 | 2.1 | 410 | 30.5 | 1.0045 | 7.3 | 12 | 2 | 2 |
| 8 F | 98–102 | 25 | 1.5 | 650 | 27.5 | 1.0039 | 7.2 | 8 | 1 | −1 |
| 8 F | 102–106 | 25 | 2.7 | 450 | 67.2 | 1.0091 | 7.0 | 13 | 4 | 2 |
| 8 F | 106–118 | 25 | 2.9 | 670 | 54 | 1.0081 | 6.5 | 10 | 2 | 3 |
| 8 F | 118–122 | 25 | 2.2 | 310 | 42.6 | 1.0064 | 7.4 | 7 | 2 | 0 |
| 8 F | 122–126 | 25 | 0.0 | 950 | 26.3 | 1.0044 | 7.1 | 3 | 1 | −1 |
| 8 F | 126–130 | 25 | 0.0 | 510 | 48.1 | 1.0065 | 6.4 | 2 | 0 | 1 |
| 8 F | Day 7 | 25 | <LOQ | NM | 38.5 | 1.0050 | 6.2 | 3 | −1 | 3 |
| 8 F | Day 8 | 25 | 0.0 | NM | 122 | 1.0177 | 5.3 | −4 | −4 | −6 |
| 8 F | Day 9 | 25 | 1.0 | NM | 202.4 | 1.0223 | 7.1 | −9 | −6 | −6 |
| 9 M | BL | 25 | 0.0 | 650 | 13.2 | 1.0028 | 7.3 | 0 | −1 | −1 |
| 9 M | 1 | 25 | 0.0 | 740 | 10.4 | 1.0017 | 6.8 | 18 | 10 | 4 |
| 9 M | 2 | 25 | 2.1 | 690 | 13.0 | 1.0023 | 7.3 | 106 | 72 | 54 |
| 9 M | 3 | 25 | 8.6 | 360 | 19.0 | 1.0037 | 7.5 | 106 | 119 | 140 |
| 9 M | 4 | 25 | 72.6 | 70 | 92.4 | 1.0099 | 7.3 | 94 | 118 | 149 |
| 9 M | 4–6 | 25 | 175 | 70 | 197.9 | 1.0182 | 5.8 | 88 | 115 | 145 |
| 9 M | 6–8 | 25 | 231.5 | 40 | 297.9 | 1.0269 | 5.9 | 77 | 105 | 133 |
| 9 M | 8–10 | 25 | 152.1 | 60 | 310.3 | 1.0290 | 5.8 | 73 | 109 | 137 |
| 9 M | 10–12 | 25 | 44.7 | 80 | 76.3 | 1.0104 | 6.0 | 97 | 116 | 145 |
| 9 M | 12–22 | 25 | 75.1 | 560 | 120.6 | 1.0146 | 6.0 | 95 | 117 | 148 |
| 9 M | 22–26 | 25 | 24.2 | 460 | 68.0 | 1.0078 | 6.7 | 103 | 120 | 146 |
| 9 M | 26–30 | 25 | 19.6 | 260 | 68.2 | 1.0100 | 7.4 | 98 | 113 | 132 |
| 9 M | 30–34 | 25 | 8.9 | 480 | 32.5 | 1.0056 | 7.4 | 105 | 64 | 46 |
| 9 M | 34–46 | 25 | 21.5 | 550 | 85.0 | 1.0122 | 7.0 | 97 | 117 | 125 |
| 9 M | 46–50 | 25 | 24.0 | 660 | 139.1 | 1.0163 | 6.4 | 93 | 112 | 140 |
| 9 M | 50–54 | 25 | 6.2 | 830 | 45.2 | 1.0071 | 7.5 | 67 | 25 | 17 |
| 9 M | 54–58 | 25 | 2.4 | 1250 | 27.6 | 1.0050 | 7.3 | 22 | 8 | 6 |
| 9 M | 58–70 | 25 | 6.1 | 1150 | 89.4 | 1.0115 | 7.0 | 71 | 25 | 18 |
| 9 M | 70–74 | 25 | 6.9 | 190 | 131.1 | 1.0130 | 6.7 | 81 | 32 | 21 |
| 9 M | 74–78 | 25 | 1.1 | 1120 | 15.4 | 1.0030 | 7.4 | 7 | 2 | −1 |
| 9 M | 78–82 | 25 | 2.0 | 470 | 40.5 | 1.0066 | 7.2 | 11 | 4 | 2 |
| 9 M | 82–94 | 25 | 2.8 | 1150 | 72.5 | 1.0105 | 7.2 | 18 | 5 | 5 |
| 9 M | 94–98 | 25 | 1.9 | 360 | 76.7 | 1.0089 | 7.2 | 11 | 5 | 1 |
| 9 M | 98–102 | 25 | <LOQ | 760 | 29.2 | 1.0065 | 7.5 | 4 | 1 | −1 |
| 9 M | 102–106 | 25 | 2.0 | 940 | 70.1 | 1.0135 | 6.9 | 7 | 2 | −2 |
| 9 M | 106–118 | 25 | <LOQ | 1650 | 60.3 | 1.0077 | 7.2 | 4 | 0 | 0 |
| 9 M | 118–122 | 25 | 1.5 | 280 | 125.8 | 1.0136 | 7.4 | 5 | 0 | 0 |
| 11 M | BL | 25 | 0.0 | 50 | 253.9 | 1.0231 | 6.4 | −13 | −8 | −7 |
| 11 M | 1 | 25 | 0.9 | 460 | 25.4 | 1.0032 | 6.5 | 94 | 53 | 41 |
| 11 M | 2 | 25 | 30.6 | 150 | 65.1 | 1.0051 | 7.1 | 97 | 116 | 158 |
| 11 M | 3 | 25 | 425.8 | 20 | 346.3 | 1.0233 | 7.2 | 77 | 109 | 154 |
| 11 M | 4 | 25 | 516.6 | 40 | 253.4 | 1.0221 | 7.2 | 84 | 107 | 153 |
| 11 M | 4–6 | 25 | 70.8 | 620 | 36.5 | 1.0041 | 6.8 | 101 | 116 | 154 |
| 11 M | 6–8 | 25 | 36.4 | 740 | 27.7 | 1.0033 | 6.9 | 96 | 111 | 149 |
| 11 M | 8–10 | 25 | 144 | 170 | 117.4 | 1.0107 | 6.3 | 91 | 108 | 150 |
| 11 M | 10–12 | 25 | 44.4 | 500 | 33.3 | 1.0040 | 6.2 | 101 | 114 | 164 |
| 11 M | 12–22 | 25 | 121.4 | 700 | 128.5 | 1.0113 | 6.6 | 90 | 105 | 156 |
| 11 M | 22–26 | 25 | 159 | 140 | 195.1 | 1.0191 | 7.4 | 83 | 108 | 151 |
| 11 M | 26–30 | 25 | 72.4 | 760 | 93.2 | 1.0129 | 7.3 | 87 | 111 | 149 |
| 11 M | 30–34 | 25 | 69.2 | 400 | 114.2 | 1.0135 | 6.5 | 89 | 113 | 159 |
| 11 M | 34–46 | 25 | 46.3 | 1150 | 113.3 | 1.0120 | 7.1 | 90 | 114 | 156 |
| 11 M | 46–50 | 25 | 20.1 | 610 | 56.0 | 1.0087 | 7.3 | 89 | 65 | 48 |
| 11 M | 50–54 | 25 | 14.4 | 1010 | 49.4 | 1.0069 | 7.0 | 91 | 37 | 27 |
| 11 M | 54–58 | 25 | 14.1 | 760 | 54.2 | 1.0067 | 6.7 | 84 | 34 | 25 |
| 11 M | 58–70 | 25 | 19.9 | 830 | 158.9 | 1.0139 | 6.4 | 82 | 71 | 60 |
| 11 M | 70–74 | 25 | 12.8 | 410 | 89.9 | 1.0120 | 7.5 | 81 | 34 | 22 |
| 11 M | 74–78 | 25 | 7.5 | 880 | 47.2 | 1.0066 | 7.2 | 36 | 15 | 8 |
| 11 M | 78–82 | 25 | 12.2 | 410 | 109.3 | 1.0129 | 6.9 | 63 | 22 | 18 |
| 11 M | 82–94 | 25 | 6.2 | 750 | 134.0 | 1.0131 | 5.9 | 48 | 13 | 12 |
| 11 M | 94–98 | 25 | 4.6 | 410 | 58.4 | 1.0096 | 7.5 | 15 | 5 | 3 |
| 11 M | 98–102 | 25 | 6.4 | 210 | 119.1 | 1.0160 | 7.3 | 21 | 5 | 3 |
| 11 M | 102–106 | 25 | 2.1 | 860 | 51.8 | 1.0056 | 6.8 | 8 | 2 | −2 |
| 11 M | 106–118 | 25 | 3.6 | 310 | 188.3 | 1.0176 | 6.8 | 13 | 4 | 1 |
| 11 M | 118–122 | 25 | 3.1 | 260 | 172.1 | 1.0169 | 6.5 | 9 | 3 | 0 |
| 11 M | 122–126 | 25 | 1.4 | 1050 | 46.2 | 1.0063 | 7.0 | 4 | 1 | −3 |
| 11 M | 126–130 | 25 | 0.0 | 260 | 20.0 | 1.0025 | 6.8 | 3 | 1 | −1 |
| 11 M | Day 7 | 25 | 3.5 | NM | 190.0 | 1.0176 | 7.4 | 4 | −1 | −4 |
| 11 M | Day 8 | 25 | 0.8 | NM | 122.4 | 1.0093 | 7.3 | 2 | −1 | 0 |
| 25 F | BL | 25 | 0.0 | 790 | 10.8 | 1.0021 | 6.6 | 2 | −1 | −7 |
| 25 F | 1 | 25 | 0.0 | 880 | 8.7 | 1.0016 | 7.2 | 5 | 2 | −3 |
| 25 F | 2 | 25 | 0.0 | 590 | 11.0 | 1.0021 | 7.5 | 71 | 35 | 17 |
| 25 F | 3 | 25 | 7.5 | 580 | 10.0 | 1.0019 | 7.5 | 108 | 101 | 63 |
| 25 F | 4 | 25 | 43.2 | 190 | 27.6 | 1.0048 | 7.5 | 108 | 150 | 160 |
| 25 F | 4–6 | 25 | 728.6 | 40 | 313.3 | 1.0293 | 5.6 | 75 | 129 | 138 |
| 25 F | 6–8 | 25 | 397.5 | 50 | 271.5 | 1.0318 | 5.5 | 77 | 127 | 138 |
| 25 F | 8–10 | 25 | 325.6 | 50 | 271.7 | 1.0320 | 5.6 | 75 | 131 | 147 |
| 25 F | 10–12 | 25 | 248.4 | 70 | 233.9 | 1.0300 | 6.3 | 77 | 127 | 142 |
| 25 F | 12–22 | 25 | 78.7 | 510 | 125.8 | 1.0143 | 6.2 | 96 | 145 | 152 |
| 25 F | 22–26 | 25 | 58.9 | 160 | 102.2 | 1.0133 | 7.4 | 96 | 143 | 158 |
| 25 F | 26–30 | 25 | 9.6 | 1260 | 21.9 | 1.0040 | 7.5 | 95 | 41 | 30 |
| 25 F | 30–34 | 25 | 8.3 | 960 | 24.4 | 1.0042 | 7.5 | 77 | 34 | 19 |
| 25 F | 34–46 | 25 | 15.4 | 1340 | 58.5 | 1.0072 | 7.5 | 105 | 65 | 34 |
| 25 F | 46–50 | 25 | 8.5 | 460 | 55.2 | 1.0061 | 5.7 | 99 | 46 | 32 |
| 25 F | 50–54 | 25 | 4.0 | 1110 | 22.4 | 1.0032 | 7.0 | 17 | 10 | 10 |
| 25 F | 54–58 | 25 | 0.0 | 1600 | 19.5 | 1.0030 | 7.1 | 13 | 6 | 1 |
| 25 F | 58–70 | 25 | 3.3 | 1500 | 42.2 | 1.0055 | 6.9 | 22 | 10 | 2 |
| 25 F | 70–74 | 25 | 0.0 | 1210 | 20.0 | 1.0029 | 7.2 | 8 | 1 | −1 |
| 25 F | 74–78 | 25 | 0.0 | 1310 | 20.3 | 1.0033 | 7.2 | 12 | 2 | 0 |
| 25 F | 78–82 | 25 | 3.2 | 550 | 44.4 | 1.0060 | 7.1 | 19 | 7 | 0 |
| 25 F | 82–94 | 25 | 3.1 | 1560 | 42.3 | 1.0060 | 7.4 | 12 | 6 | −1 |
| 25 F | 94–98 | 25 | 3.3 | 325 | 69.1 | 1.0074 | 6.4 | 15 | 7 | 1 |
| 27 F | BL | 25 | 0.0 | 310 | 22.9 | 1.0048 | 5.9 | −2 | −3 | −5 |
| 27 F | 1 | 25 | 0.0 | 170 | 35.6 | 1.0068 | 5.8 | 56 | 28 | 14 |
| 27 F | 2 | 25 | 3.5 | 290 | 18.4 | 1.0036 | 6.1 | 106 | 132 | 96 |
| 27 F | 3 | 25 | 9.2 | 250 | 19.8 | 1.0038 | 6.0 | 108 | 143 | 137 |
| 27 F | 4 | 25 | 12.4 | 220 | 17.5 | 1.0034 | 6.0 | 105 | 145 | 114 |
| 27 F | 4–6 | 25 | 39.7 | 240 | 64.2 | 1.0093 | 5.8 | 102 | 143 | 156 |
| 27 F | 6–8 | 25 | 74.8 | 100 | 156.2 | 1.0192 | 5.7 | 91 | 137 | 153 |
| 27 F | 8–10 | 25 | 38.7 | 170 | 103 | 1.0122 | 5.8 | 98 | 139 | 149 |
| 27 F | 10–12 | 25 | 18.5 | 320 | 51.9 | 1.0074 | 5.9 | 103 | 142 | 148 |
| 27 F | 12–22 | 25 | 0.0 | 460 | 87.3 | 1.0106 | 5.8 | 100 | 141 | 160 |
| 27 F | 22–26 | 25 | 33.3 | 310 | 122.7 | 1.0144 | 5.5 | 94 | 140 | 153 |
| 27 F | 26–30 | 25 | 32.4 | 80 | 136.9 | 1.0170 | 5.6 | 89 | 135 | 151 |
| 27 F | 30–34 | 25 | 20.8 | 460 | 62.3 | 1.0081 | 5.9 | 100 | 147 | 153 |
| 27 F | 34–46 | 25 | 12.5 | 1060 | 56.7 | 1.0072 | 6.1 | 104 | 125 | 78 |
| 27 F | 46–50 | 25 | 7.2 | 400 | 45.8 | 1.0060 | 6.1 | 95 | 41 | 25 |
| 27 F | 50–54 | 25 | 5.5 | 60 | 40.4 | 1.0057 | 7.3 | 61 | 26 | 11 |
| 27 F | 54–58 | 25 | 17.5 | 50 | 233.6 | 1.0203 | 5.6 | 84 | 133 | 130 |
| 27 F | 58–70 | 25 | 5.8 | 750 | 100.3 | 1.0113 | 6.2 | 69 | 28 | 20 |
| 27 F | 70–74 | 25 | 1.4 | 860 | 27.5 | 1.0050 | 6.8 | 11 | 5 | 1 |
| 27 F | 74–78 | 25 | 3.6 | 210 | 127.9 | 1.0165 | 6.8 | 26 | 9 | 1 |
| 27 F | 78–82 | 25 | 2.6 | 70 | 127.6 | 1.0163 | 6.7 | 20 | 7 | 2 |
| 27 F | 82–94 | 25 | 3.0 | 610 | 120.3 | 1.0154 | 6.2 | 13 | 3 | 4 |
| 27 F | 94–98 | 25 | 1.7 | 80 | 135.7 | 1.0182 | 5.9 | 5 | 0 | −3 |
| 4 F | BL | 50 | 0.0 | 350 | 12.4 | 1.0018 | 6.9 | 4 | 2 | 1 |
| 4 F | 1 | 50 | 0.0 | 450 | 11.7 | 1.0018 | 6.7 | 18 | 6 | 5 |
| 4 F | 2 | 50 | 6.2 | 380 | 27.8 | 1.0031 | 6.2 | 109 | 100 | 102 |
| 4 F | 3 | 50 | 215.5 | 60 | 171.1 | 1.0237 | 6.1 | 86 | 102 | 136 |
| 4 F | 4 | 50 | 102.4 | 120 | 52.7 | 1.0101 | 7.3 | 104 | 104 | 144 |
| 4 F | 4–6 | 50 | 26.1 | 420 | 14.2 | 1.0028 | 7.5 | 112 | 84 | 72 |
| 4 F | 6–8 | 50 | 30.5 | 420 | 23.7 | 1.0048 | 7.5 | 108 | 88 | 77 |
| 4 F | 8–10 | 50 | 29.6 | 520 | 29.5 | 1.0056 | 7.4 | 108 | 95 | 90 |
| 4 F | 10–12 | 50 | 16.9 | 490 | 21.6 | 1.0040 | 7.4 | 109 | 59 | 48 |
| 4 F | 12–22 | 50 | 57.5 | 270 | 129.1 | 1.0130 | 7.0 | 98 | 107 | 141 |
| 4 F | 22–26 | 50 | 34.5 | 320 | 60.9 | 1.0082 | 7.4 | 107 | 101 | 135 |
| 4 F | 26–30 | 50 | 6.4 | 370 | 20.5 | 1.0041 | 7.3 | 99 | 34 | 26 |
| 4 F | 30–34 | 50 | 5.9 | 1550 | 17.3 | 1.0035 | 7.2 | 72 | 23 | 16 |
| 4 F | 34–46 | 50 | 13.6 | 450 | 84.0 | 1.0117 | 6.8 | 104 | 98 | 90 |
| 4 F | 46–50 | 50 | 9.3 | 1620 | 31.2 | 1.0047 | 7.0 | 106 | 40 | 33 |
| 4 F | 50–54 | 50 | 5.9 | 1600 | 17.6 | 1.0029 | 7.0 | 57 | 19 | 16 |
| 4 F | 54–58 | 50 | 5.4 | 1250 | 19.6 | 1.0035 | 7.0 | 49 | 16 | 13 |
| 4 F | 58–70 | 50 | 10.5 | 650 | 87.7 | 1.0093 | 6.7 | 104 | 47 | 38 |
| 4 F | 70–74 | 50 | 4.2 | 1000 | 24.8 | 1.0032 | 7.2 | 33 | 11 | 10 |
| 4 F | 74–78 | 50 | 7.2 | 900 | 27.5 | 1.0046 | 7.0 | 45 | 13 | 12 |
| 4 F | 78–82 | 50 | 8.0 | 350 | 68.6 | 1.0111 | 6.8 | 64 | 23 | 17 |
| 4 F | 82–94 | 50 | 10.8 | 500 | 135.1 | 1.0151 | 6.8 | 86 | 31 | 27 |
| 4 F | 94–98 | 50 | 3.0 | 290 | 37.9 | 1.0048 | 7.2 | 22 | 9 | 8 |
| 4 F | 98–102 | 50 | 1.4 | 900 | 20.6 | 1.0036 | 7.4 | 9 | 3 | 4 |
| 4 F | 102–106 | 50 | 1.7 | 830 | 29.2 | 1.0049 | 7.3 | 9 | 4 | 1 |
| 4 F | 106–118 | 50 | 1.2 | 230 | 216.6 | 1.0222 | 6.4 | −6 | −2 | −3 |
| 4 F | 118–122 | 50 | 1.0 | 320 | 30.2 | 1.0046 | 7.4 | 6 | 3 | 2 |
| 4 F | 122–126 | 50 | 2.0 | 60 | 66.6 | 1.0111 | 7.5 | 7 | 2 | 0 |
| 7 M | BL | 50 | 0.0 | 490 | 19.1 | 1.0030 | 6.4 | 0 | −2 | −1 |
| 7 M | 1 | 50 | 0.0 | 490 | 16.5 | 1.0027 | 6.4 | 11 | 5 | 4 |
| 7 M | 2 | 50 | 7.8 | 480 | 24.0 | 1.0036 | 7.2 | 103 | 114 | 141 |
| 7 M | 3 | 50 | 275.2 | 20 | 134.0 | 1.0125 | 6.4 | 92 | 111 | 148 |
| 7 M | 4 | 50 | 392.3 | 80 | 148.4 | 1.0134 | 6.2 | 90 | 110 | 148 |
| 7 M | 4–6 | 50 | 87.2 | 740 | 27.9 | 1.0039 | 6.9 | 101 | 115 | 150 |
| 7 M | 6–8 | 50 | 83.7 | 700 | 27.1 | 1.0043 | 7.4 | 101 | 115 | 150 |
| 7 M | 8–10 | 50 | 153.6 | 410 | 50.3 | 1.0072 | 7.2 | 99 | 113 | 145 |
| 7 M | 10–12 | 50 | 108.3 | 500 | 39.3 | 1.0053 | 7.2 | 101 | 115 | 148 |
| 7 M | 12–22 | 50 | 557.6 | 510 | 169.8 | 1.0141 | 6.2 | 92 | 114 | 148 |
| 7 M | 22–26 | 50 | 334.5 | 310 | 109.4 | 1.0113 | 5.9 | 94 | 109 | 148 |
| 7 M | 26–30 | 50 | 93.6 | 910 | 34.3 | 1.0043 | 6.1 | 101 | 111 | 152 |
| 7 M | 30–34 | 50 | 96.4 | 860 | 39.9 | 1.0053 | 6.6 | 99 | 115 | 155 |
| 7 M | 34–46 | 50 | 289.2 | 760 | 111.6 | 1.0122 | 6.2 | 91 | 106 | 148 |
| 7 M | 46–50 | 50 | 113.3 | 410 | 52.2 | 1.0053 | 7.4 | 102 | 114 | 147 |
| 7 M | 50–54 | 50 | 51.4 | 950 | 39.8 | 1.0059 | 7.5 | 99 | 113 | 114 |
| 7 M | 54–58 | 50 | 71.7 | 760 | 56.6 | 1.0072 | 7.3 | 99 | 111 | 146 |
| 7 M | 58–70 | 50 | 88.1 | 860 | 76.7 | 1.0083 | 6.3 | 96 | 110 | 146 |
| 7 M | 70–74 | 50 | 80.1 | 360 | 86.9 | 1.0086 | 7.4 | 96 | 113 | 145 |
| 7 M | 74–78 | 50 | 19.2 | 1160 | 23.8 | 1.0033 | 7.3 | 98 | 41 | 31 |
| 7 M | 78–82 | 50 | 30.9 | 900 | 34.1 | 1.0045 | 7.2 | 101 | 74 | 54 |
| 7 M | 82–94 | 50 | 98.2 | 720 | 132.7 | 1.0126 | 6.0 | 94 | 110 | 148 |
| 7 M | 94–98 | 50 | 49.3 | 210 | 96.4 | 1.0082 | 7.4 | 95 | 107 | 97 |
| 7 M | 98–102 | 50 | 37.8 | 400 | 72.2 | 1.0089 | 7.5 | 93 | 83 | 63 |
| 7 M | 102–106 | 50 | 23.8 | 900 | 58.4 | 1.0074 | 7.1 | 96 | 47 | 35 |
| 7 M | 106–118 | 50 | 37.5 | 1000 | 96.5 | 1.0091 | 7.0 | 95 | 81 | 57 |
| 7 M | 118–122 | 50 | 17.8 | 640 | 52.7 | 1.0055 | 7.5 | 90 | 32 | 24 |
| 7 M | 122–126 | 50 | 14.4 | 1690 | 42.8 | 1.0059 | 7.4 | 73 | 24 | 19 |
| 7 M | 126–130 | 50 | 10.2 | 900 | 34.8 | 1.0044 | 6.5 | 48 | 17 | 15 |
| 7 M | Day 7 | 50 | 23.3 | NM | 103.3 | 1.0121 | 7.6 | 89 | 35 | 27 |
| 7 M | Day 8 | 50 | 11.0 | NM | 90.4 | 1.0131 | 7.3 | 39 | 14 | 10 |
| 7 M | Day 9 | 50 | 5.5 | NM | 58.2 | 1.0105 | 6.9 | 13 | 3 | 3 |
| 17 F | BL | 50 | 0.0 | 320 | 26.6 | 1.0038 | 6.6 | 1 | −1 | −1 |
| 17 F | 1 | 50 | 0.0 | 730 | 8.8 | 1.0016 | 7.1 | 13 | 4 | 3 |
| 17 F | 2 | 50 | 22.4 | 560 | 12.6 | 1.0022 | 7.4 | 113 | 122 | 131 |
| 17 F | 3 | 50 | 379.2 | 130 | 54.6 | 1.0079 | 7.3 | 107 | 122 | 153 |
| 17 F | 4 | 50 | NS | NS | NS | NS | NS | NS | NS | NS |
| 17 F | 4–6 | 50 | 193.1 | 570 | 19.8 | 1.0034 | 7.4 | 113 | 125 | 159 |
| 17 F | 6–8 | 50 | 108.5 | 880 | 11.8 | 1.0026 | 7.5 | 114 | 124 | 158 |
| 17 F | 8–10 | 50 | 416.2 | 190 | 57.0 | 1.0091 | 7.5 | 103 | 123 | 153 |
| 17 F | 10–12 | 50 | 314.3 | 280 | 54.4 | 1.0093 | 7.4 | 106 | 119 | 153 |
| 17 F | 12–22 | 50 | 969.3 | 380 | 210.9 | 1.0235 | 6.6 | 87 | 114 | 151 |
| 17 F | 22–26 | 50 | 160.8 | 670 | 32.1 | 1.0062 | 7.5 | 109 | 124 | 161 |
| 17 F | 26–30 | 50 | 108.2 | 620 | 28.7 | 1.0057 | 7.4 | 107 | 120 | 156 |
| 17 F | 30–34 | 50 | 52.3 | 1100 | 20.3 | 1.0049 | 7.4 | 110 | 114 | 94 |
| 17 F | 34–46 | 50 | 65.9 | 1410 | 50.7 | 1.0085 | 7.3 | 105 | 122 | 143 |
| 17 F | 46–50 | 50 | 53.1 | 470 | 46.8 | 1.0081 | 7.5 | 108 | 110 | 96 |
| 17 F | 50–54 | 50 | 15.8 | 1090 | 15.7 | 1.0032 | 7.5 | 78 | 25 | 21 |
| 17 F | 54–58 | 50 | 12.4 | 1300 | 18.9 | 1.0044 | 7.4 | 77 | 25 | 20 |
| 17 F | 58–70 | 50 | 23.9 | 1460 | 36.8 | 1.0064 | 7.3 | 108 | 46 | 34 |
| 17 F | 70–74 | 50 | 18.4 | 950 | 28.1 | 1.0047 | 7.5 | 96 | 34 | 25 |
| 17 F | 74–78 | 50 | 6.4 | 1510 | 12.3 | 1.0034 | 7.4 | 25 | 8 | 7 |
| 17 F | 78–82 | 50 | 7.7 | 1020 | 20.9 | 1.0047 | 7.4 | 33 | 12 | 10 |
| 17 F | 82–94 | 50 | 12.5 | 1010 | 52.6 | 1.0077 | 7.3 | 51 | 17 | 13 |
| 17 F | 94–98 | 50 | 5.6 | 90 | 41.1 | 1.0064 | 7.5 | 24 | 9 | 7 |
| 17 F | 98–102 | 50 | 3.4 | 730 | 31.1 | 1.0062 | 7.6 | 16 | 5 | 5 |
| 17 F | 102–106 | 50 | 1.9 | 910 | 18.2 | 1.0036 | 7.3 | 8 | 1 | 1 |
| 17 F | 106–118 | 50 | 1.0 | 1170 | 229.7 | 1.0224 | 6.4 | −7 | −6 | −9 |
| 17 F | 118–122 | 50 | 2.5 | 690 | 20.9 | 1.0030 | 7.2 | 10 | 1 | 2 |
| 17 F | 122–126 | 50 | 0.0 | 1410 | 15.6 | 1.0032 | 7.5 | 6 | −1 | 0 |
| 17 F | 126–130 | 50 | 2.6 | 510 | 45.1 | 1.0088 | 7.4 | 6 | 1 | 1 |
| 17 F | Day 7 | 50 | 3.4 | NM | 72.3 | 1.0089 | 7.3 | 10 | 3 | 1 |
| 17 F | Day 8 | 50 | <LOQ | NM | 23.5 | 1.0028 | 7.3 | 4 | 1 | −2 |
| 17 F | Day 9 | 50 | 1.1 | NM | 47.9 | 1.0057 | 7.2 | 2 | −1 | −3 |
| 19 M | BL | 50 | 0.0 | 450 | 18.6 | 1.0033 | 6.1 | 5 | 5 | 3 |
| 19 M | 1 | 50 | 0.0 | 670 | 13.2 | 1.0024 | 5.9 | 23 | 12 | 10 |
| 19 M | 2 | 50 | 0.0 | 820 | 11.6 | 1.0024 | 7.1 | 104 | 74 | 56 |
| 19 M | 3 | 50 | 20.0 | 750 | 13.1 | 1.0026 | 7.2 | 107 | 123 | 128 |
| 19 M | 4 | 50 | 49.2 | 560 | 18.7 | 1.0034 | 7.3 | 104 | 128 | 157 |
| 19 M | 4–6 | 50 | 191.2 | 420 | 42.6 | 1.0069 | 7.1 | 102 | 124 | 153 |
| 19 M | 6–8 | 50 | 1024.8 | 100 | 198.8 | 1.0204 | 5.7 | 86 | 119 | 147 |
| 19 M | 8–10 | 50 | 773.2 | 50 | 332.9 | 1.0260 | 5.5 | 81 | 117 | 154 |
| 19 M | 10–12 | 50 | 767.1 | 50 | 289.1 | 1.0456 | 5.6 | 85 | 117 | 146 |
| 19 M | 12–22 | 50 | 525.3 | 370 | 251.9 | 1.0226 | 5.6 | 84 | 117 | 145 |
| 19 M | 22–26 | 50 | 455.6 | 160 | 245.2 | 1.0243 | 5.8 | 85 | 118 | 150 |
| 19 M | 26–30 | 50 | 157.8 | 220 | 137.4 | 1.0193 | 6.7 | 89 | 118 | 148 |
| 19 M | 30–34 | 50 | 67.7 | 380 | 106.4 | 1.0144 | 5.5 | 91 | 122 | 154 |
| 19 M | 34–46 | 50 | 76.3 | 670 | 147.6 | 1.0173 | 5.8 | 93 | 121 | 153 |
| 19 M | 46–50 | 50 | 64.6 | 560 | 77.8 | 1.0109 | 7.5 | 98 | 122 | 142 |
| 19 M | 50–54 | 50 | 21.9 | 1060 | 34.5 | 1.0059 | 7.4 | 101 | 59 | 42 |
| 19 M | 54–58 | 50 | 70.8 | 260 | 143.9 | 1.0191 | 6.6 | 91 | 118 | 142 |
| 19 M | 58–70 | 50 | 60.6 | 700 | 154.2 | 1.0179 | 6.0 | 91 | 121 | 134 |
| 19 M | 70–74 | 50 | 25.9 | 560 | 76.6 | 1.0107 | 7.5 | 99 | 67 | 47 |
| 19 M | 74–78 | 50 | 10.3 | 520 | 41.0 | 1.0065 | 6.5 | 65 | 26 | 23 |
| 19 M | 78–82 | 50 | 16.3 | 650 | 63.8 | 1.0091 | 6.8 | 85 | 37 | 30 |
| 19 M | 82–94 | 50 | 30.6 | 950 | 136.1 | 1.0167 | 6.2 | 94 | 77 | 55 |
| 19 M | 94–98 | 50 | 31.1 | 210 | 203.4 | 1.0193 | 7.5 | 89 | 74 | 54 |
| 19 M | 98–102 | 50 | 20.1 | 240 | 173.7 | 1.0208 | 7.6 | 80 | 37 | 29 |
| 19 M | 102–106 | 50 | 12.1 | 340 | 108.3 | 1.0163 | 7.4 | 54 | 24 | 17 |
| 19 M | 106–118 | 50 | 11.8 | 460 | 165.0 | 1.0181 | 6.6 | 58 | 25 | 19 |
| 19 M | 118–122 | 50 | 7.6 | 60 | 107.5 | 1.0149 | 7.5 | 31 | 16 | 13 |
| 19 M | 122–126 | 50 | 0.0 | 560 | 56.3 | 1.0097 | 7.2 | 12 | 9 | 7 |
| 19 M | 126–130 | 50 | 0.0 | 420 | 56.9 | 1.0092 | 7.5 | 10 | 8 | 6 |
| 19 M | Day 7 | 50 | 8.2 | NM | 160.1 | 1.0202 | 7.2 | 24 | 12 | 10 |
| 19 M | Day 8 | 50 | 5.2 | NM | 205.3 | 1.0214 | 7.5 | 11 | 7 | 7 |
| 23 M | BL | 50 | 0.0 | 80 | 185.4 | 1.0235 | 6.9 | −8 | −5 | −5 |
| 23 M | 1 | 50 | 0.0 | 380 | 38.3 | 1.0063 | 7.1 | 85 | 41 | 33 |
| 23 M | 2 | 50 | 21.7 | 550 | 19.2 | 1.0026 | 7.0 | 103 | 115 | 145 |
| 23 M | 3 | 50 | 145.4 | 240 | 44.6 | 1.0062 | 7.2 | 97 | 118 | 155 |
| 23 M | 4 | 50 | 681.2 | 60 | 183.3 | 1.0198 | 6.2 | 82 | 112 | 148 |
| 23 M | 4–6 | 50 | 165.6 | 550 | 42.7 | 1.0053 | 6.3 | 99 | 122 | 153 |
| 23 M | 6–8 | 50 | 68.2 | 400 | 23.9 | 1.0032 | 7.1 | 100 | 115 | 155 |
| 23 M | 8–10 | 50 | 238.9 | 250 | 95.3 | 1.0105 | 6.9 | 96 | 119 | 155 |
| 23 M | 10–12 | 50 | 182.4 | 100 | 97.1 | 1.0104 | 6.2 | 95 | 113 | 150 |
| 23 M | 12–22 | 50 | 520.3 | 200 | 327.1 | 1.0250 | 6.1 | 78 | 109 | 143 |
| 23 M | 22–26 | 50 | 46.5 | 260 | 30.3 | 1.0046 | 7.5 | 101 | 115 | 116 |
| 23 M | 26–30 | 50 | 38.6 | 1060 | 31.3 | 1.0053 | 7.5 | 99 | 114 | 107 |
| 23 M | 30–34 | 50 | 64.0 | 960 | 71.4 | 1.0088 | 7.1 | 97 | 118 | 149 |
| 23 M | 34–46 | 50 | 95.6 | 410 | 253.3 | 1.0226 | 6.1 | 80 | 108 | 148 |
| 23 M | 46–50 | 50 | 62.8 | 310 | 135.1 | 1.0167 | 7.5 | 88 | 111 | 117 |
| 23 M | 50–54 | 50 | 29.8 | 410 | 95.9 | 1.0128 | 7.4 | 91 | 74 | 52 |
| 23 M | 54–58 | 50 | 13.4 | 600 | 57.4 | 1.0078 | 7.2 | 68 | 24 | 21 |
| 23 M | 58–70 | 50 | 25.8 | 560 | 192.3 | 1.0157 | 6.5 | 89 | 63 | 47 |
| 23 M | 70–74 | 50 | 17.6 | 160 | 169.4 | 1.0173 | 7.3 | 83 | 36 | 27 |
| 23 M | 74–78 | 50 | 6.7 | 210 | 70.3 | 1.0088 | 6.9 | 30 | 10 | 10 |
| 23 M | 78–82 | 50 | 4.5 | 740 | 52.2 | 1.0072 | 7.0 | 18 | 8 | 7 |
| 23 M | 82–94 | 50 | 4.6 | 950 | 114.3 | 1.0114 | 6.8 | 19 | 9 | 7 |
| 23 M | 94–98 | 50 | 8.3 | 380 | 161.0 | 1.0162 | 7.4 | 30 | 1 | 10 |
| 23 M | 98–102 | 50 | 3.0 | 480 | 82.1 | 1.0113 | 7.4 | 8 | 4 | 3 |
| 24 F | BL | 50 | 0.0 | 290 | 34.7 | 1.0046 | 6.7 | 1 | −3 | −3 |
| 24 F | 1 | 50 | 0.0 | 360 | 17.2 | 1.0024 | 7.0 | 79 | 38 | 22 |
| 24 F | 2 | 50 | 22.2 | 200 | 22.6 | 1.0029 | 7.3 | 109 | 150 | 160 |
| 24 F | 3 | 50 | NS | NS | NS | NS | NS | NS | NS | NS |
| 24 F | 4 | 50 | 655.8 | 70 | 158.5 | 1.0166 | 6.7 | 95 | 142 | 161 |
| 24 F | 4–6 | 50 | NS | NS | NS | NS | NS | NS | NS | NS |
| 24 F | 6–8 | 50 | 826.9 | 170 | 133.4 | 1.0153 | 6.9 | 97 | 146 | 161 |
| 24 F | 8–10 | 50 | 353.0 | 200 | 52.5 | 1.007 | 7.0 | 106 | 147 | 157 |
| 24 F | 10–12 | 50 | 541.0 | 80 | 105.6 | 1.0148 | 7.0 | 97 | 143 | 153 |
| 24 F | 12–22 | 50 | 535.4 | 310 | 141.1 | 1.0180 | 7.1 | 93 | 138 | 158 |
| 24 F | 22–26 | 50 | 196.8 | 320 | 60.7 | 1.0121 | 7.5 | 96 | 145 | 156 |
| 24 F | 26–30 | 50 | 124.5 | 310 | 61.1 | 1.0107 | 7.5 | 100 | 141 | 155 |
| 24 F | 30–34 | 50 | 69.2 | 510 | 33.0 | 1.0068 | 7.5 | 106 | 144 | 154 |
| 24 F | 34–46 | 50 | 83.6 | 1100 | 74.5 | 1.0101 | 7.4 | 104 | 146 | 152 |
| 24 F | 46–50 | 50 | 113.2 | 220 | 234.2 | 1.0191 | 6.3 | 89 | 137 | 159 |
| 24 F | 50–54 | 50 | 53.3 | 260 | 57.5 | 1.0069 | 7.4 | 104 | 146 | 152 |
| 24 F | 54–58 | 50 | 96.0 | 300 | 116.0 | 1.0154 | 7.5 | 96 | 141 | 157 |
| 24 F | 58–70 | 50 | 60.4 | 590 | 122.2 | 1.0146 | 7.4 | 97 | 140 | 151 |
| 24 F | 70–74 | 50 | 56.3 | 240 | 269.8 | 1.0232 | 6.6 | 84 | 136 | 145 |
| 24 F | 74–78 | 50 | 93.1 | 310 | 162.5 | 1.0188 | 7.6 | 94 | 140 | 152 |
| 24 F | 78–82 | 50 | 32.8 | 400 | 63.6 | 1.0087 | 7.5 | 105 | 110 | 67 |
| 24 F | 82–94 | 50 | 34.3 | 720 | 85.7 | 1.0101 | 7.2 | 101 | 129 | 78 |
| 24 F | 94–98 | 50 | 39.8 | 80 | 265.4 | 1.0227 | 5.9 | 83 | 138 | 153 |
| 24 F | 98–102 | 50 | 58.5 | 220 | 179.9 | 1.0154 | 7.4 | 97 | 140 | 137 |
| 24 F | 102–106 | 50 | 34.8 | 210 | 159.8 | 1.0168 | 7.1 | 95 | 125 | 85 |
| 24 F | 106–118 | 50 | 41.7 | 510 | 145.4 | 1.0180 | 7.3 | 94 | 131 | 91 |
| 24 F | 118–122 | 50 | 37.3 | 120 | 182.8 | 1.0182 | 6.3 | 96 | 126 | 91 |
| 24 F | 122–126 | 50 | 36.8 | 230 | 113.2 | 1.0135 | 7.4 | 97 | 108 | 64 |
| 24 F | 126–130 | 50 | 14.4 | 520 | 45.9 | 1.0071 | 7.4 | 70 | 30 | 18 |
| 24 F | Day 7 | 50 | 34.2 | NM | 226.4 | 1.0213 | 6.7 | 92 | 116 | 72 |
| 24 F | Day 8 | 50 | 14.9 | NM | 131.8 | 1.0171 | 6.9 | 68 | 32 | 17 |
| 24 F | Day 9 | 50 | 6.1 | NM | 75.4 | 1.0085 | 6.6 | 30 | 13 | 6 |
Note: Participant IDs including “M” or “F” to indicate Male or Female; NS, no sample obtained; <LOQ indicates samples where THCCOOH was detected, but was below the limit of quantitation; Data are reported through the last specimen in which GC/MS values for THCCOOH > LOD and all subsequent “negative” specimens omitted for parsimony; sample volume was not measured on outpatient days (Days 7–9) and is denoted by “NM”.
Figure 1.
Mean THCCOOH urine specimen concentrations following ingestion of cannabis brownies containing 10-, 25- and 50-mg doses of THC. Error bars represent ± standard error of the mean.
Table III.
Mean THCCOOH maximum concentrations (Cmax), times of maximum concentration (Tmax) and ranges across individuals in urine specimens following ingestion of cannabis brownies.
| THC dose (mg) | THCCOOH Cmax (ng/mL) | THCCOOH Tmax (h) |
|---|---|---|
| 10 | 106.8 (33.8–277.9) | 8.2 (4–17) |
| 25 | 335.1 (74.8–728.6) | 5.8 (4–7) |
| 50 | 712.55 (215.5–1024.8) | 9.2 (3–17) |
Note: The midpoint of the collection time period was used to quantify the time point of pooled specimens.
Mean detection times to the first and last positive urine specimens confirmed by GC/MS (THCCOOH ≥ 15 ng/mL) are presented in Table IV. Overall, time to first positive ranged between 2 and 5 h after drug administration. On average, the amount of time that elapsed between dosing and confirmation of the first positive urine specimen was longer for the 10 mg THC dose (mean = 4.2 h; range = 3–5 h) and decreased in a monotonic fashion for the 25 (mean = 3.5 h; range = 2–5 h) and 50 mg THC doses (mean = 2.5 h; range = 2–3 h), respectively. A similar dose-orderly pattern was observed for time to last positive (Table IV). Compared to the 10 mg (44.7 h; range = 28–72 h) and 25 mg THC doses (mean = 52.0 h; range = 40–64 h), time to last positive was greatest for the 50 mg THC dose (mean = 93.3 h; range = 24–146 h). For two participants randomized to the 50 mg dose (Participant #7, Participant #24), THCCOOH values that exceeded the 15 ng/mL GC/MS cutoff were still evident at the Day 7 time point.
Table IV.
Mean THCCOOH detection times and ranges across individuals by dose in urine specimens following ingestion of cannabis brownies.
| THC dose (mg) | THCCOOH GC/MS (h) (cutoff = 15 ng/mL) |
|---|---|
| Detection time (h) to first positive, mean (range) | |
| 10 | 4.2 (3–5) |
| 25 | 3.5 (2–5) |
| 50 | 2.5 (2–3) |
| Detection time (h) to last positive, mean (range) | |
| 10 | 44.7 (28–72) |
| 25 | 52.0 (40–64) |
| 50 | 93.3 (24–146) |
Note: The midpoint of the collection time period was used to quantify the time point of pooled specimens.
Sensitivity, specificity and agreement
A detailed summary of sensitivity, specificity, and agreement values is included in Table V and categorized by separate comparisons of the 20, 50 and 100 ng/mL IA outcomes relative to the GC/MS results. The IA 20 ng/mL cutoff was observed to have the greatest proportion of TPs evidenced by a sensitivity value of 99.6%. In contrast, the IA 100 ng/mL cutoff was associated with the smallest proportion of TPs but was also the cutoff value that corresponded to the highest number of TNs. Overall, the IA 50 ng/mL cutoff value produced the most balanced levels of sensitivity, specificity and agreement (all >90%).
Table V.
Comparisons of immunoassay responses to GC/MS confirmation analyses in urine specimens following ingestion of cannabis brownies.
| Urine THCCOOH IA (cutoff = 20 ng/mL) vs. THCCOOH GC/MS (cutoff = 15 ng/mL) | Urine THCCOOH IA (cutoff = 50 ng/mL) vs. THCCOOH GC/MS (cutoff = 15 ng/mL) | Urine THCCOOH IA (cutoff = 100 ng/mL) vs. THCCOOH GC/MS (cutoff = 15 ng/mL) | |
|---|---|---|---|
| # True positive (%) | 226 (40) | 210 (37) | 161 (28) |
| # True negative (%) | 199 (35) | 315 (55) | 333 (59) |
| # False positive (%) | 142 (25) | 26 (5) | 8 (1) |
| # False negative (%) | 1 (0.2) | 17 (3) | 66 (12) |
| N | 568 | 568 | 568 |
| % Sensitivity | 99.6 | 92.5 | 70.9 |
| % Specificity | 58.4 | 92.4 | 97.7 |
| % Agreement | 74.8 | 92.4 | 87.0 |
Discussion
Attaining a comprehensive understanding of the urinary excretion profile of THCCOOH following oral cannabis administration has implications that span multiple domains. Urine remains the primary biological matrix for most instances of drug testing, and is utilized for workplace drug testing programs, forensic toxicology testing, and clinical testing in substance use treatment programs and randomized clinical trials (25). The present study examined the excretion profile of THCCOOH in urine for 9 days following ingestion of a cannabis brownie that contained either a 10, 25 or 50 mg dose of THC. Participants had previously used cannabis, but not in the prior 3 months (mean time since last use was 24.2 months), and none had detectable THCCOOH in urine at baseline. Following acute dose administration, maximum urinary THCCOOH concentrations (Cmax) and time to last positive test (using 50 ng/mL immunoassay screening and 15 ng/mL GC/MS confirmation cutoffs) increased as a function of THC dose in an orderly manner. Substantial between-subject variability was observed for Cmax, Tmax and time to last positive test result. Following administration of the 50 mg THC dose, two of six participants had urine samples that tested positive 1 week after exposure (Day 7 of the study).
Some notable differences were observed in the current study compared with results of previously published studies on acute cannabis effects via the oral and smoked routes of administration. Cone et al. (21) examined the excretion profile and detection times of THCCOOH in participants (N = 5) who ingested a brownie made with cannabis-containing 22 or 45 mg of THC. The range of Cmax THCCOOH concentrations observed in the present study for the 25 mg (mean 335 ng/mL; range = 75–729 ng/mL) and 50 mg doses (mean 713 ng/mL; range=216–1,025 ng/mL) were greater than the ranges observed by Cone et al. for 22 (range = 108–325 ng/mL) and 45 mg (range = 177–436 ng/mL) THC dose conditions. Similarly, maximum THCCOOH concentrations (Cmax) among individuals who ingested the 25 mg dose in the present study were predominantly higher than maximum individual THCCOOH concentrations (222, 117 and 167 ng/mL, respectively) obtained from three participants following ingestion of a cannabis brownie reported to contain 20–25 mg THC (22). The reason for these differences may be due to brownie preparation procedures. We prepared several test batches of cannabis brownies prior to conducting experimental sessions with human participants; when the cannabis was not pre-heated prior to baking (e.g., 21, 22), only ~50% of THC-A converted to THC in test brownies. Thus, the dose of active THC may have been greater in the present study, relative to the prior two studies, despite comparable amounts of total THC concentration (THC-A + THC) in the raw cannabis used to prepare the brownies. Also, notable individual differences were observed in all prior investigations, and while small sample sizes explain variation across studies, the commonly observed pattern of interindividual variability may also be attributed to body mass index (i.e., THC is highly lipophilic) and individual differences in metabolism (26).
Compared with prior studies evaluating smoked cannabis pharmacokinetics at comparable doses, urine THCCOOH results in the present study showed higher Cmax values and longer time to last positive test. Using a within-subjects design, Huestis et al. (27) evaluated the urinary excretion profile of THCCOOH for 1 week after participants smoked marijuana cigarettes containing 16 or 34 mg total THC. Average maximum THCCOOH values (Cmax) of 90 ng/mL (range = 21–234 ng/mL) and 153 ng/mL (range = 30–355 ng/mL) were observed 8 (±1 h) and 14 (±4 h) hours following smoked administration of the lower and higher doses, respectively. Mannoet al. (28) conducted a similar investigation that employed a within-subjects design and compared THCCOOH concentrations after smoked administration of 15 and 27 mg THC doses. In that study the observed maximum THCCOOH concentrations were 94 ng/mL (±63 ng/mL) and 179 ng/mL (±147 ng/mL) 4 h after smoked administration. These differences are also consistent with a study by ElSohly et al. in which THCCOOH concentrations in urine were significantly greater following oral administration of 15 mg THC (dronabinol) compared with smoked cannabis containing ~17 mg THC (20).
Currently, federal urine drug testing guidelines for the detection of recent cannabis use require an initial cutoff concentration of 50 ng/mL measured via THCCOOH immunoassay (IA) and a confirmatory cutoff concentration value of 15 ng/mL measured via GC/MS or liquid chromatography/mass spectrometry (LC/MS) (25). In the current investigation, we evaluated the results of three THCCOOH IAs at three separate cutoffs (20, 50 and 100 ng/mL) relative to a GC/MS confirmatory cutoff of 15 ng/mL. The IA cutoff of 50 ng/mL yielded the highest sensitivity, specificity and agreement values (92.5%, 92.4% and 92.4%, respectively). Not surprisingly, the 20 ng/mL cutoff was associated with the highest false-positive rate (25.0%), and conversely, the 100 ng/mL cutoff was associated with highest false-negative rate (11.6%). In circumstances where high-sensitivity rates are favored (i.e., true positives) through the use of a 20 ng/mL IA cutoff, rates of false positives increase and agreement between IA and GC/MS is substantially reduced.
Strengths and limitations
The current investigation was designed to circumvent the limitations of previously published work that examined the pharmacokinetics of urinary THCCOOH following oral cannabis self-administration. The current study had several notable strengths compared to prior studies. First, the sample was comprised of both men and women distributed equally across the three dose conditions, while prior reports are primarily from samples that were predominantly male, or the characteristics of study participants were not reported. Second, study participants endorsed prior exposure to cannabis, but denied use of cannabis and products containing hemp for at least 3 months, and all tested negative for cannabis use prior to study participation. This allowed for evaluation of the true window of detection of a single cannabis exposure via oral ingestion without confounding effects via urinary excretion of residual cannabinoids. Third, this study involved precise administration of three THC doses in a controlled laboratory setting, followed by 6 days of continuous participant monitoring and urine collection during which complete abstinence from cannabis, or other substances that may influence results was ensured. This was followed by three additional days of outpatient data collection.
Limitations of the study are that only one type of cannabis product was administered, a relatively homogeneous and small sample of participants was used, and considerable inter-subject variability was observed. Thus, caution is warranted for use of these data to interpret urinary THCCOOH excretion profiles for cannabis ingested in other product types, such as gum, hard candy or liquid beverages that may differ in the rate of THC absorption. These data also may not be representative of THCCOOH excretion among children, elderly or individuals concurrently using medications that impact CYP450 enzymes.
Conclusion
Ingestion of cannabis brownies containing 10, 25 and 50 mg doses of THC produced urine specimens that contained detectable levels of the THC metabolite, THCCOOH, for up to 9 days following initial dose exposure in healthy adult participants without recent cannabis use. Maximum THCCOOH concentrations (Cmax) increased as THC dose increased. Individual values for Cmax and Tmax pharmacokinetic parameters were highly variable, but variability was not related to sex. Analysis of THCCOOH detection times also revealed a dose-related pattern; ingestion of the 50 mg THC dose decreased average time to first positive and increased average detection time to last positive compared with lower THC doses. Review of GC/MS-confirmed immunoassays with 20, 50 and 100 ng/mL cutoffs demonstrated that the 50 ng/mL value, which is the recommended cutoff utilized by federal workplace drug testing programs, produced excellent sensitivity, specificity and agreement rates. In light of the limitations of published studies that examined the urine excretion profile following oral cannabis self-administration, the present study incorporated a rigorous highly controlled design that included healthy participants without a recent history of cannabis use to reduce the confounding effects of residual excretion of cannabinoid metabolites resulting from prior exposure to non-study cannabis. Future research is required to characterize urine THCCOOH excretion profiles to assess concentrations and detection windows among frequent cannabis users, older adults, those with compromised drug metabolism, cannabis administered via different vehicles (e.g., cannabis placed in various foodstuffs, consumed with high fat versus low-fat meals) and to evaluate the impacts of body mass or, for females, menstrual cycle/hormones.
Acknowledgments
Dr Cone is a consultant to the Division of Workplace Programs, Substance Abuse and Mental Health Services Administration (SAMHSA) and has an Adjunct Professor appointment with Johns Hopkins University School of Medicine, Baltimore, MD. Drs Vandrey and Bigelow are faculty and Dr Schlienz is a post-doctoral fellow at Johns Hopkins University School of Medicine, Baltimore, MD. Dr Herrmann is now a Principal Research Scientist at Battelle Memorial Institute. Dr Mitchell is an employee of RTI International, and Mr LoDico and Mr Flegel are employees of SAMHSA. We thank the support staff of the Johns Hopkins University Behavioral Pharmacology Research Unit and Clinical Research Unit for outstanding contributions to the implementation of this study.
Funding
This study was funded by the Substance Abuse and Mental Health Services Administration (SAMHSA). The National Institute on Drug Abuse (NIDA) provided material support for the study (cannabis) and financial support for the participation of Dr Schlienz and Dr Herrmann (T32-DA07209). We also obtained clinical services support from Grant UL1-RR025005 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research.
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