| Popis: |
Objective: To assess the effect of orlistat on the pharmacokinetics of pravastatin. Methods: Arandomised, double-blind, placebo-controlled, two-period crossover study was conducted in 24 otherwise healthy males with mild hypercholesterolaemia. In period 1, study participants were randomised to receive pravastatin 40mg once every evening plus placebo three times daily or pravastatin 40mg once every evening plus orlistat 120mg three times daily for 6 days. Following a 9-day washout period, patients switched treatment regimens for an additional 6 days in period 2. Serial blood samples were collected before and at appropriate intervals after the evening dose of study medications on day 6 of each study period. Results: Comparing orlistat with placebo regimens, differences in pravastatin mean area under the concentration-time curve from 0 to 12 hours (AUC0–12h) [57.8 ± 22.8 vs 55.6 ± 23.5 μg/L · h] and maximum plasma concentration (Cmax) [31.1 ± 15.4 vs 28.8 ± 15.4 μg/L] were 4 and 9%, respectively (p > 0.05). The 90% confidence intervals for the least square means of the ratio of orlistat to placebo treatment were within ±20% for AUC0–12hand within ±30% for Cmax. These results indicated that orlistat had no significant impact on the pharmacokinetics of pravastatin. Concomitant administration with orlistat for 6 days did not significantly alter the lipid-lowering effect of pravastatin. Comparing orlistat with placebo regimens, the percentage decreases from baseline in low density lipoprotein (LDL)-cholesterol (−34.6 vs −33.5%, respectively) and total cholesterol (−23.8 vs −22.5%, respectively) were similar after 6 days’ treatment. Conclusion: No pharmacokinetic or pharmacodynamic interactions between orlistat and pravastatin were detected. |
