Table 2.
PK Parameters Observed During Drug‐Drug Interaction Studies in Healthy Subjects
| Reference (Study Type) | Treatment | Plasma Analyte | Cmax, Mean (% CV), ng/mL | Tmax, Median (range), h | AUC0‐inf, Mean (% CV), ng•h/mL | t½, Mean (% CV), h | Vd/F, Mean (% CV), L | CL/F, Mean (% CV), L/hr |
|---|---|---|---|---|---|---|---|---|
| OV‐102163 (effect on CLB with CYP3A or CYP2C19 inhibitor) | 10 mg CLB + 400 mg KTZ | CLB | 190 (21) | 2.0 (0.5‐2.5) | 6432 (19) | 41.7 (32) | 94 (27) | 1.6 (20) |
| N‐CLB | 38 (43) | 84 (48‐120) | 7851 (61) | 74.0 (44) | ND | ND | ||
| 10 mg CLB | CLB | 224 (18) | 1.0 (0.5‐2.6) | 4360 (29) | 37.5 (32) | 128 (30) | 2.5 (32) | |
| N‐CLB | 38 (37) | 60 (36‐84) | 6987 (70) | 67.5 (36) | ND | ND | ||
| 10 mg CLB + 40 mg OPZ | CLB | 211 (21) | 1.3 (0.5‐4.0) | 5398 (21) | 36.7 (32) | 98 (24) | 1.9 (18) | |
| N‐CLB | 47 (34) | 60 (48‐84) | 9176 (85) | 66.7 (83) | ND | ND | ||
| 10 mg CLB | CLB | 218 (15) | 1.0 (0.5‐4) | 4239 (31) | 31.8 (37) | 107 (14) | 2.5 (23) | |
| N‐CLB | 39 (24) | 42 (24‐84) | 5549 (50) | 54.4 (38) | ND | ND | ||
| OV‐102363 (effect of CLB on CYP probe substrates) | Drug Cocktail | Caffeine | 5486 (24) | 0.5 (0.3‐1.5) | 38 528 (33) | 5.9 (26) | 46 (18) | 5.7 (32) |
| Drug Cocktail + CLB | 4676 (24) | 0.8 (0.3‐2.0) | 40 622 (29) | 6.3 (20) | 46 (17) | 5.4 (31) | ||
| Drug Cocktail | Tolbutamide | 50 806 (12) | 3.5 (1.5‐6.0) | 841 599 (35) | 10.0 (36) | 8.7 (16) | 0.7 (28) | |
| Drug Cocktail + CLB | 47 511 (13) | 3.5 (2.0‐6.0) | 746 043 (35) | 9.3 (37) | 9.0 (14) | 0.7 (27) | ||
| Drug Cocktail | Dextromethorphan | 6 (116) | 2.0 (1.0‐6.0) | 208 (235) | 14.4 (122) | 19 707 (76) | 2142 (107) | |
| Drug Cocktail + CLB | 7 (91) | 3.0 (2.0‐8.0) | 214 (205) | 14.0 (113) | 10 374 (75) | 983 (93) | ||
| Drug Cocktail | Midazolam | 20 (53) | 0.5 (0.3‐1.0) | 43 (44) | 3.9 (37) | 581 (43) | 107 (36) | |
| Drug Cocktail + CLB | 15 (43) | 0.5 (0.3‐1.0) | 31 (37) | 3.6 (29) | 687 (33) | 141 (29) |
AUC0‐inf, area under the plasma drug concentration‐time curve extrapolated to infinity; CLB, clobazam; CL/F, apparent clearance; Cmax, maximum plasma concentration; CV, coefficient of variation; CYP, cytochrome P450 enzyme; KTZ, ketoconazole; N‐CLB, N‐desmethylclobazam; ND, not determined; OPZ, omeprazole; t1/2, elimination half‐life of drug; Tmax, time to Cmax; Vd/F, apparent volume of distribution.