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Table 3 Statistical comparisons of pharmacokinetic parameters following a single dose of substrates

From: Assessment of Pharmacokinetic Interactions Between Obeticholic Acid and Caffeine, Midazolam, Warfarin, Dextromethorphan, Omeprazole, Rosuvastatin, and Digoxin in Phase 1 Studies in Healthy Subjects

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)
  1. 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