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To assess the influence of orlistat, a lipase inhibitor, on the absorption of β-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 β-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 β-carotene to determine plasma concentrations of unchanged β-carotene. Short-term (3 to 6 days) treatment with orlistat did not alter endogenous profiles of β-carotene in plasma. When β-carotene was given during orlistat treatment, its absorption was reduced by approximately one-third. This reduction was consistent for all three dose levels of β-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 β-carotene will be absorbed during orlistat treatment; this may be sufficient to achieve physiologic levels of β-carotene with an appropriate dose of β-carotene, should supplementation be needed in obese patients who have developed β-carotene deficiency during therapy with orlistat.