Effect of the lipase inhibitor orlistat on the pharmacokinetics of four different antihypertensive drugs in healthy volunteers.
OBJECTIVE
To study the influence of the lipase inhibitor orlistat on the pharmacokinetics of the antihypertensive drugs atenolol, furosemide, captopril and nifedipine.


METHODS
Four open-label, crossover studies were performed on six to eight healthy male volunteers. Orlistat was given in doses of 50 mg 3 times daily mid-meal for 7 (nifedipine and captopril) or 8 days (atenolol and furosemide). The four antihypertensive drugs (atenolol 100-mg tablet, furosemide 40-mg tablet, captopril 50-mg tablet and nifedipine 20-mg slow-release tablet) were administered in single doses twice, once before and once together, with orlistat at the end of the orlistat treatment period.


RESULTS
The plasma concentration time profiles and the pharmacokinetic parameters estimated for these drugs were in the expected range, except for furosemide, whose bioavailability was lower than reported in the literature. This was probably due to the fact that furosemide was given during a meal. There were minor, but statistically significant, differences in one of the pharmacokinetic parameters of furosemide and nifedipine (no difference for captopril and atenolol) when these drugs were given alone and in combination with orlistat: the half-life of furosemide was slightly longer, the time to peak plasma concentrations of nifedipine was slightly longer. None of these are considered to be clinically significant changes.


CONCLUSIONS
The lipase inhibitor orlistat given 50 mg 3 times daily does not alter the pharmacokinetics of atenolol, furosemide, nifedipine and captopril to a clinically significant extent.
Weber
C
C
F. Hoffmann-La Roche Ltd., Department of Clinical Pharmacology, Clinical Research and Development, Basel, Switzerland.
Tam
Y K
YK
Schmidtke-Schrezenmeier
G
G
Jonkmann
J H
JH
van Brummelen
P
P
D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D001262:Atenolol / Q000097:blood / Q000493:pharmacokinetics; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics; D002216:Captopril / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004232:Diuretics / Q000097:blood / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D009543:Nifedipine / Q000097:blood / Q000493:pharmacokinetics; D000077403:Orlistat
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D004791:Enzyme Inhibitors; D007783:Lactones; D001262:Atenolol; D005665:Furosemide; D000077403:Orlistat; D002216:Captopril; D009543:Nifedipine