Table 1.
Overview of clinical drug–drug interaction studies with oral OCA in healthy, fasted subjects
| Study | OCA administration | Probe substrate administration | CYP/transporter | ||
|---|---|---|---|---|---|
| Dose | Days | Probe substrate (oral dose) | Days | ||
| I | 10 and 25 mg QD | Day 5 through day 23 |
Caffeine (200 mg) Midazolam (2 mg) |
Day 3 and day 21 Day 1 and day 19 |
CYP1A2 CYP3A |
| II | 10 and 25 mg QD | Day 8 through day 27 | Warfarin (25 mg) | Day 1, day 21 |
CYP2C9 (S-warfarin) CYP1A2, CYP3A (R-warfarin) |
| III | 10 and 25 mg QD | Day 5 through day 28 |
Dextromethorphan (30 mg) Omeprazole (20 mg) |
Day 1, day 18 Day 4, day 21–28 |
CYP2D6 CYP2C19 |
| IV | 10 and 25 mg QD | Day 6 through day 23 | Rosuvastatin (20 mg) | Day 1, day 19 | BCRP/OATP1B1/OATP1B3 |
| V | 10 and 25 mg QD | Day 6 through day 23 | Digoxin (0.25 mg) | Day 1, day 19 | P-gp (MDR1) |
BCRP breast cancer resistance protein, CYP cytochrome P450, MDR1 multidrug resistance protein 1, OATP organic anion transporting polypeptide, QD once daily