Table 3.
Statistical comparisons of pharmacokinetic parameters following a single dose of substrates
| Treatment | 10 mg OCA | 25 mg OCA | ||
|---|---|---|---|---|
| n | GLSM ratio (90% CI) | n | GLSM ratio (90% CI) | |
| Study I: caffeine (CYP1A2) | ||||
| AUC∞ (h ng/mL) | 24 | 1.417 (1.350–1.488) | 21 | 1.654 (1.557–1.757) |
| C max (ng/mL) | 24 | 1.061 (1.014–1.111) | 21 | 1.099 (1.043–1.159) |
| Study I: midazolam (CYP3A) | ||||
| AUC∞ (h ng/mL) | 23 | 1.020 (0.930–1.119) | 23 | 1.259 (1.135–1.397) |
| C max (ng/mL) | 24 | 1.017 (0.919–1.126) | 23 | 1.173 (1.052–1.309) |
| Study II: S-warfarin (CYP2C9) | ||||
| AUC∞ (h ng/mL) | 21 | 1.126 (1.097–1.155) | 22 | 1.181 (1.142–1.220) |
| C max (ng/mL) | 21 | 1.120 (1.052–1.193) | 22 | 1.058 (0.990–1.131) |
| Study II: R-warfarin (CYP1A2 and 3A4) | ||||
| AUC∞ (h ng/mL) | 21 | 1.209 (1.163–1.256) | 22 | 1.324 (1.274–1.375) |
| C max (ng/mL) | 21 | 1.109 (1.042–1.181) | 22 | 1.052 (0.985–1.123) |
| Study III: dextromethorphan (CYP2D6) | ||||
| AUC∞ (h ng/mL) | 19 | 0.891 (0.747–1.063) | 19 | 0.895 (0.785–1.021) |
| C max (ng/mL) | 23 | 0.879 (0.725–1.065) | 24 | 0.826 (0.728–0.937) |
| Study III: omeprazole (CYP2C19) | ||||
| AUC∞ (h ng/mL) | 21 | 1.321 (1.217–1.434) | 19 | 1.366 (1.242–1.502) |
| C max (ng/mL) | 23 | 1.327 (1.167–1.508) | 24 | 1.148 (0.965–1.366) |
| Study IV: rosuvastatin (BCRP/OATP1B1/OATP1B3) | ||||
| AUC∞ (h ng/mL) | 24 | 1.219 (1.125–1.321) | 23 | 1.296 (1.158–1.450) |
| C max (ng/mL) | 24 | 1.272 (1.150–1.408) | 24 | 1.258 (1.092–1.451) |
| Study V: digoxin (P-gp) | ||||
| AUC∞ (h ng/mL) | 24 | 1.012 (0.954–1.073) | 24 | 1.073 (0.994–1.157) |
| C max (ng/mL) | 24 | 0.967 (0.869–1.076) | 24 | 1.236 (1.083–1.411) |
AUC ∞ area under plasma concentration–time curve from time zero to infinity, BCRP breast cancer resistance protein, CI confidence interval, C max maximum plasma concentration, CYP cytochrome P450, GLSM geometric least square means, OATP organic anion transporting polypeptide, OCA obeticholic acid, PK pharmacokinetic