Table 7.
Summary of plasma acetazolamide, THC, OH-THC and COOH-THC pharmacokinetic parameters (pharmacokinetic parameters analysis set)
| Parameter | Acetazolamide (RLD) 250 mg fasted | Dronabinol (RLD) 5 mg fasted | IHL-42X fasted | IHL-42X fed | ||||
|---|---|---|---|---|---|---|---|---|
| n | Gmean (Geo CV%) | n | Gmean (Geo CV%) | n | Gmean (Geo CV%) | n | Gmean (Geo CV%) | |
| Analyte: Acetazolamide (ng/mL) | ||||||||
| Cmax (ng/mL) | 119 | 13100 (27.0) | – | – | 121 | 7720 (38.5) | 117 | 9620 (37.8) |
| Tmax (h)a | 119 | 1.50 (0.50, 6.05) | – | – | 121 | 3.50 (1.50, 12.0) | 117 | 4.00 (1.03, 24.0) |
| AUC0–last (h × ng/mL) | 119 | 91700 (14.6) | – | 121 | 79900 (26.6) | 117 | 83400 (28.5) | |
| AUC0–inf (h × ng/mL) | 119 | 94400 (14.9) | – | – | 118 | 84600 (25.9) | 115 | 86400 (28.3) |
| AUC%extrap (%) | 119 | 2.51 (51.3) | – | – | 118 | 4.18 (62.6) | 115 | 2.93 (53.8) |
| AUC0–12 (h × ng/mL) | 119 | 66400 (14.5) | – | – | 121 | 48200 (35.5) | 117 | 47900 (46.6) |
| AUC0–24 (h × ng/mL) | 119 | 82800 (14.1) | – | – | 121 | 67400 (29.5) | 117 | 71700 (30.3) |
| T1/2 (h) | 119 | 10.1 (16.3) | – | – | 120 | 11.4 (24.8) | 115 | 9.50 (15.4) |
| Kel (/h) | 119 | 0.0685 (16.3) | – | – | 120 | 0.0609 (24.8) | 115 | 0.0730 (15.4) |
| CL/F (L/h) | 119 | 2.65 (14.9) | – | – | 118 | 2.96 (25.9) | 115 | 2.90 (28.3) |
| Vz/F (L) | 119 | 38.7 (21.7) | – | – | 118 | 47.7 (33.8) | 115 | 39.7 (36.2) |
| Analyte: THC (ng/mL) | ||||||||
| Cmax (ng/mL) | – | – | 118 | 1.67 (59.8) | 114 | 1.48 (70.0) | 114 | 3.61 (72.3) |
| Tmax (h)a | – | – | 118 | 1.00 (0.50, 4.00) | 114 | 1.00 (0.50, 6.00) | 114 | 2.50 (1.00, 16.1) |
| AUC0–last (h × ng/mL) | – | – | 118 | 2.32 (64.1) | 114 | 2.07 (77.4) | 114 | 9.28 (57.0) |
| AUC0–inf (h × ng/mL) | – | – | 96 | 2.77 (45.7) | 71 | 2.75 (48.7) | 82 | 10.2 (49.4) |
| AUC%extrap (%) | – | – | 96 | 8.27 (41.1) | 71 | 8.65 (53.4) | 82 | 3.86 (58.7) |
| AUC0–12 (h × ng/mL) | – | – | 114 | 2.63 (52.8) | 100 | 2.57 (57.3) | 107 | 9.49 (53.7) |
| AUC0–24 (h × ng/mL) | – | – | 114 | 2.66 (54.2) | 99 | 2.59 (58.2) | 103 | 10.2 (51.8) |
| T1/2 (h) | – | – | 104 | 1.13 (40.2) | 85 | 1.26 (55.8) | 84 | 1.80 (66.9) |
| Kel (/h) | – | – | 104 | 0.615 (40.2) | 85 | 0.551 (55.8) | 84 | 0.385 (66.9) |
| CL/F (L/h) | – | – | 96 | 1810 (45.7) | 71 | 1820 (48.7) | 82 | 492 (49.4) |
| Vz/F (L) | – | – | 96 | 2840 (45.7) | 71 | 2900 (51.0) | 82 | 1220 (57.2) |
| Analyte: OH-THC (ng/mL) | ||||||||
| Cmax (ng/mL) | – | – | 118 | 2.08 (59.3) | 120 | 1.95 (61.2) | 116 | 2.20 (59.3) |
| Tmax (h)a | – | – | 118 | 1.50 (0.50, 4.00) | 120 | 1.50 (0.50, 6.00) | 116 | 2.50 (1.00, 16.1) |
| AUC0–last (h × ng/mL) | – | – | 118 | 5.74 (65.4) | 120 | 5.31 (71.3) | 116 | 10.0 (52.6) |
| AUC0–inf (h × ng/mL) | – | – | 110 | 6.73 (60.0) | 97 | 6.54 (67.0) | 105 | 12.0 (46.6) |
| AUC%extrap (%) | – | – | 110 | 10.8 (36.3) | 97 | 11.4 (32.9) | 105 | 10.0 (40.3) |
| AUC0–12 (h × ng/mL) | – | – | 117 | 5.80 (53.0) | 119 | 5.29 (58.3) | 116 | 8.60 (47.7) |
| AUC0–24 (h × ng/mL) | – | – | 117 | 6.37 (57.7) | 119 | 5.97 (62.9) | 115 | 10.6 (44.8) |
| T1/2 (h) | – | – | 114 | 3.95 (68.3) | 115 | 4.31 (74.1) | 111 | 6.11 (49.0) |
| Kel (/h) | – | – | 114 | 0.176 (68.3) | 115 | 0.161 (74.1) | 111 | 0.113 (49.0) |
| CL/F (L/h) | – | – | 110 | 743 (60.0) | 97 | 765 (67.0) | 105 | 418 (46.6) |
| Vz/F (L) | – | – | 110 | 4080 (39.9) | 97 | 4480 (35.6) | 105 | 3620 (37.9) |
| Analyte: COOH-THC (ng/mL) | ||||||||
| Cmax (ng/mL) | – | – | 118 | 18.7 (37.2) | 120 | 17.5 (38.5) | 115 | 14.1 (45.6) |
| Tmax (h)a | – | – | 118 | 1.50 (1.00, 4.00) | 120 | 1.64 (1.00, 6.00) | 115 | 3.00 (1.02, 16.1) |
| AUC0–last (h × ng/mL) | – | – | 118 | 149 (54.0) | 120 | 139 (59.4) | 115 | 164 (50.6) |
| AUC0–inf (h × ng/mL) | – | – | 29 | 204 (44.3) | 29 | 174 (57.0) | 19 | 233 (51.2) |
| AUC%extrap (%) | – | – | 29 | 16.6 (17.2) | 29 | 15.6 (17.0) | 19 | 16.6 (13.8) |
| AUC0–12 (h × ng/mL) | – | – | 118 | 83.7 (40.4) | 120 | 76.8 (41.0) | 115 | 77.7 (43.1) |
| AUC0–24 (h × ng/mL) | – | – | 118 | 118 (43.0) | 120 | 109 (44.2) | 115 | 120 (41.0) |
| T1/2 (h) | – | – | 85 | 22.0 (47.4) | 84 | 20.1 (65.6) | 74 | 22.9 (54.9) |
| Kel (/h) | – | – | 85 | 0.0315 (47.4) | 84 | 0.0344 (65.6) | 74 | 0.0302 (54.9) |
| CL/F (L/h) | – | – | 29 | 24.5 (44.3) | 29 | 28.7 (57.0) | 19 | 21.4 (51.2) |
| Vz/F (L) | – | – | 29 | 577 (32.3) | 29 | 566 (24.7) | 19 | 485 (36.6) |
PK parameters are defined in Table 2
AUC0–last area under the drug concentration-time curve, from time zero to time of the last measurable concentration, AUC0–inf AUC from time zero extrapolated to infinity, AUC0–12h AUC from time zero to 12 h, AUC0–24h AUC from time zero to 24 h, AUC%extrap percentage of AUC that was extrapolated beyond last observed data point, CL/F apparent total plasma clearance, COOH-THC 11-nor- Δ9-tetrahydrocannabinol-carboxylic acid, Cmax maximum plasma concentration, geo CV geometric coefficient of variation, gmean geometric mean, n number of participants with observations, Kel (/h) elimination rate constant, SD standard deviation, OH-THC 11-hydroxy-Δ9-tetrahydrocannabinol, RLD reference listed drug (taro acetazolamide and marinol), t1/2 time to reach Cmax, THC Δ9-tetrahydrocannabinol, Vz/F apparent terminal volume of distribution
aData are presented as geometric mean (geo CV%) except for Tmax, which is presented as median (minimum, maximum)