. 2021 May 5;10(11):1279–1289. doi: 10.1002/cpdd.950

Table 3.

Statistical Analysis of the Pharmacokinetic Parameters of Caffeine and Paraxanthine Following Administration of Caffeine + Placebo (Day 1) and of Caffeine + CBD (Day 26) — PK Analysis Set

		Geometric LS Means				Ratio Test/Reference
Analyte	PK Parameter	n	Reference	n	Test	Estimate	90%CI
Primary analysis
Caffeine	C_max ^a (ng/mL)	16	4600	9	5269	1.15	1.04‐1.26
	AUC_0‐t ^a (ng·h/mL)	16	39 969	9	75 237	1.88	1.56‐2.27
	AUC_0‐∞ ^a (ng·h/mL)	16	40 856	9	79 718	1.95	1.62‐2.35
	t_max ^b (h)	9	1.5	9	3.0	0.58	0.01‐1.50
Paraxanthine	C_max ^a (ng/mL)	16	1227	7	961	0.78	0.72‐0.86
	AUC_0‐t ^a (ng·h/mL)	16	21 454	7	23 579	1.10	0.96‐1.26
	AUC_0‐∞ ^a (ng·h/mL)	16	22 972	7	27 038	1.18	1.03‐1.35
	t_max ^b (h)	7	8.00	7	14.00	3.49	0.48‐6.00
Sensitivity analysis
Caffeine	C_max ^a (ng/mL)	16	4600	6	5460	1.19	1.03‐1.36
	AUC_0‐t ^a (ng·h/mL)	16	39 969	6	71 265	1.78	1.39‐2.29
	AUC_0‐∞ ^a (ng·h/mL)	16	40 856	6	76 272	1.87	1.45‐2.41
	t_max ^b (h)	6	2.3	6	3.0	0.57	0.00‐1.25
Paraxanthine	C_max ^a (ng/mL)	16	1227	6	984	0.80	0.73‐0.88
	AUC_0‐t ^a (ng·h/mL)	16	21 454	6	22 526	1.05	0.93‐1.18
	AUC_0‐∞ ^a (ng·h/mL)	16	22 972	6	26 023	1.13	0.99‐1.30
	t_max ^b (h)	6	8.0	6	14.0	3.99	−0.02 to 7.00

AUC_0‐t, area under the plasma concentration‐time curve up to time t, where t is the last point with a concentration above the lower limit of quantification; AUC_0‐∞, area under the plasma concentration‐time curve from time 0 to infinity; CBD, cannabidiol; CI, confidence interval; C_max, maximum (peak) concentration of drug in blood plasma; LS, least squares; PK, pharmacokinetic; t_max, (observed) time after drug administration at which peak plasma concentration occurs.

Note: Reference, caffeine + placebo treatment; test, caffeine + CBD treatment.

^{^a}

AUC and C_max, the interaction effect was explored using a mixed‐effects (analysis of variance) model with treatment as fixed factor and subject as a random effect.

^{^b}

t_max, nonparametric Wilcoxon signed rank test presenting the Hodges‐Lehman estimate and 90%CI based on the Tukey method. Median, median of the difference, and approximate 90%CI for the difference are presented.