EFFECT OF THE LIPASE INHIBITOR ORLISTAT ON THE PHARMACOKINETICS OF 4 DIFFERENT ANTIHYPERTENSIVE DRUGS IN HEALTHY-VOLUNTEERS

Objective: To study the influence of the lipase inhibitor orlistat on the pharmacokinetics of the antihypertensive drugs atenolol, furosemid e, captopril and nifedipine. Methods: Four open-label, crossover studi es were performed on six to eight healthy male volunteers. Orlistat wa s given in doses of 50 mg 3 times daily mid-meal for 7 (nifedipine and captopril) or 8 days (atenolol and furosemide). The four antihyperten sive drugs (atenolol 100-mg tablet, furosemide 40-mg tablet, captopril 50-mg tablet and nifedipine 20-mg slow-release tablet) were administe red in single doses twice, once before and once together, with orlista t at the end of the orlistat treatment period. Results: The plasma con centration time profiles and the pharmacokinetic parameters estimated for these drugs were in the expected range, except for furosemide, who se bioavailability was lower than reported in the literature. This was probably due to the fact that furosemide was given during a meal. The re were minor, but statistically significant, differences in one of th e pharmacokinetic parameters of furosemide and nifedipine (no differen ce for captopril and atenolol) when these drugs were given alone and i n combination with orlistat: the half-life of furosemide was slightly longer, the time to peak plasma concentrations of nifedipine was sligh tly longer. None of these are considered to be clinically significant changes. Conclusions: The lipase. inhibitor orlistat given 50 mg 3 tim es daily does not alter the pharmacokinetics of atenolol, furosemide, nifedipine and captopril to a clinically significant extent.