Table 3.
Summary of suvorexant pharmacokinetic parameters following administration of suvorexant alone or co-administered with the strong CYP3A inhibitor ketoconazole, moderate CYP3A inhibitor diltiazem, or the strong CYP3A inducer rifampin in healthy subjects
| Pharmacokinetic parameter | Study P008 | Study P038 | ||||
|---|---|---|---|---|---|---|
| Diltiazem sub-study | Rifampin sub-study | |||||
| Suvorexant 4 mg (N = 10) | Suvorexant 4 mg + ketoconazole (N = 10) | Suvorexant 20 mg (N = 20) | Suvorexant 20 mg + diltiazem (N = 18) | Suvorexant 40 mg (N = 10) | Suvorexant 40 mg + rifampin (N = 10)a | |
| GM AUC0–∞ (95% CI), μM·hb | 2.61 (1.84, 3.71) | 7.28 (5.13, 10.32) | 7.88 (6.57, 9.46) | 16.13 (13.38, 19.44) | 13.63 (10.53, 17.64) | 1.68 (1.30, 2.17) |
| GM Cmax (95% CI), μMb | 0.28 (0.22, 0.35) | 0.34 (0.27, 0.43) | 0.62 (0.54, 0.71) | 0.76 (0.66, 0.87) | 0.85 (0.70, 1.03) | 0.31 (0.25, 0.37) |
| Harmonic mean t½ (jack-knife SD), h | 11.2 (4.2) | 19.4 (6.9) | 12.4 (3.3) | 16.1 (5.3) | 12.9 (2.2) | 7.7 (3.4) |
| Median tmax (range), h | 1.0 (0.5–2.0) | 2.0 (1.0–4.0) | 1.5 (1.0–4.0) | 2.0 (1.0–4.0) | 2.0 (0.5–4.0) | 1.0 (0.5–2.0) |
AUC0–∞ area under the plasma concentration–time curve from time zero to infinity, CI confidence interval, Cmax maximum plasma concentration, CYP cytochrome P450, GM geometric mean, h hours, ln natural log, LSM least-squares mean, SD standard deviation, t½ half-life, tmax time to maximum plasma concentration
For one subject, the 36-h time point (Period 2) was excluded from the pharmacokinetic analysis due to an unusually high spike in plasma concentration relative to the 24-h time point data
Back-transformed LSM and CI from mixed-effects model performed on ln-transformed values