The effect of orlistat, an inhibitor of dietary fat absorption, on the pharmacokinetics of beta-carotene in healthy volunteers.
To assess the influence of orlistat, a lipase inhibitor, on the absorption of beta-carotene, an open-label, parallel, placebo-controlled, randomized, two-way crossover study was performed in 48 healthy volunteers between the ages of 19 and 58 years. Each subject received a single oral dose of 0, 30, 60, or 120 mg beta-carotene (12 subjects per dose level) on the fourth day of treatment with orlistat (120 mg) or placebo 3 times a day for 6 days. The treatments were separated by a washout period of at least 5 weeks. Serial blood samples were collected before and at appropriate intervals after administration of beta-carotene to determine plasma concentrations of unchanged beta-carotene. Short-term (3 to 6 days) treatment with orlistat did not alter endogenous profiles of beta-carotene in plasma. When beta-carotene was given during orlistat treatment, its absorption was reduced by approximately one-third. This reduction was consistent for all three dose levels of beta-carotene studied; however, the results for the 30-mg dose level were subject to greater variability, particularly for area under the concentration-time curve (AUC). It was concluded that two thirds of a supplemental dose of beta-carotene will be absorbed during orlistat treatment; this may be sufficient to achieve physiologic levels of beta-carotene with an appropriate dose of beta-carotene, should supplementation be needed in obese patients who have developed beta-carotene deficiency during therapy with orlistat.
Zhi
J
J
Hoffmann-La Roche, Inc., Nutley, New Jersey 07110-1199, USA.
Melia
A T
AT
Koss-Twardy
S G
SG
Arora
S
S
Patel
I H
IH
D000042:Absorption / Q000187:drug effects; D000284:Administration, Oral; D000328:Adult; D000975:Antioxidants / Q000032:analysis / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007783:Lactones / Q000493:pharmacokinetics / Q000494:pharmacology*; D008049:Lipase / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D000077403:Orlistat; D010919:Placebos; D012016:Reference Values; D015203:Reproducibility of Results; D019207:beta Carotene / Q000097:blood / Q000493:pharmacokinetics*
D000975:Antioxidants; D004041:Dietary Fats; D004791:Enzyme Inhibitors; D007783:Lactones; D010919:Placebos; D019207:beta Carotene; D000077403:Orlistat; D008049:Lipase