The effect of fluvoxamine on the pharmacokinetics, safety, and tolerability of ramosetron in healthy subjects

Objective To investigate the effects of multiple doses of fluvoxamine on the pharmacokinetics, safety, and tolerability of a single oral 10-mu g dose of ramosetron. Methods This was a single-center, open, one-sequence cross-over study. On Day 1, healthy male and female subjects were administered a single dose of 10 mu g ramosetron. Dosing of fluvoxamine started with an initial morning dose of 50 mg on Day 3, followed by a twice daily (12-h interval) dosing of 50 mg on Days 4-12. The morning dose on Day 11 was administered in combination with a single dose of 10 mu g ramosetron. Results Co-administration of fluvoxamine with ramosetron resulted in an increase in the C(max) and AUC(0-inf) of ramosetron by 1.42-fold (90% CI 1.35-1.49) and 2.78-fold (90% CI 2.53-3.05), respectively. Conclusion Co-administration of the CYP1A2 inhibitor fluvoxamine with ramosetron resulted in an interaction. However, the safety data collected during the study do not indicate that this interaction will cause any major safety concerns.