LACK OF EFFECT OF ORLISTAT ON THE BIOAVAILABILITY OF A SINGLE-DOSE OFNIFEDIPINE EXTENDED-RELEASE TABLETS (PROCARDIA-XL) IN HEALTHY-VOLUNTEERS

Orlistat, a lipase inhibitor, reduces dietary fat absorption, and thus could potentially alter the absorption of some concomitantly administ ered drugs, such as the nifedipine gastrointestinal therapeutic system (GITS). To assess the effect of orlistat on the bioavailability of ni fedipine GITS, a third party-blind, placebo-controlled, randomized, tw o-way crossover study was performed in 18 healthy volunteers. Each par ticipant received single 60-mg oral doses of nifedipine GITS (Procardi a XL; Pfzer Labs, New York, NY) on the fourth day of treatment with 12 0 mg of orlistat or placebo three times a day for 6 days. The two trea tments were separated by a washout period of at least 1 week. Serial b lood samples were collected before and at appropriate intervals after each nifedipine dose to determine plasma concentrations of nifedipine. The 90% confidence intervals for the ratio of geometric least-square means for maximum concentration (C-max) and area under the concentrati on-lime curve (AUC(0-t)) and for the difference of arithmetic least-sq uare means for rime to maximum concentration (t(max)) indicate that th e bioavailability of nifedipine was not altered by treatment with orli stat. Therapeutic doses of 120 mg of orlistat three times daily do not significantly alter the bioavailability of a single 60-mg oral dose o f nifedipine GITS in healthy volunteers.