PIII-67Effect of orlistat on the pharmacokinetic of rimonabant

Abstract

BACKGROUND Rimonabant is the first selective CB1 blocker developed for the management of multiple cardiometabolic risk factors in overweight/obese patients. AIMS To assess the effect of repeated doses of orlistat on the pharmacokinetics (PK) of rimonabant. METHODS This was a two-treatment, single-sequence, crossover study in 13 healthy males. Subjects received 20 mg of rimonabant on Day 1 of Period 1 and Day 4 of Period 2 and 120 mg 3 times daily of orlistat from Days 1 to 6 in Period 2. Blood samples were collected up to 336 hours after rimonabant dose in each period. Plasma was analyzed for rimonabant with a validated LC-MS/MS method. Non-compartmental PK parameters were calculated. RESULTS Mean (SD) and ratio of the geometric means (90% confidence interval, CI) for rimonabant PK parameters are as follows: (See Table) Parameter Rimonabant alone (N=13) Rimonabant + orlistat (N=12) Ratio (90% CI) Cmax(ng/mL) 211 (95) 129 (50) 0.720 (0.550, 0.941) AUClast(ng.h/mL) 2990 (1160) 3300 (1500) 1.069 (0.954, 1.199) AUC(ng.h/mL) 3520 (1400) 3230 (1290) 1.025 (0.926, 1.136) The 90% CI for AUClast and AUC were within the bioequivalence limits of 0.80 to 1.25. There was a slight reduction in rimonabant Cmax when administered with orlistat. CONCLUSIONS Orlistat had no appreciable effect on the PK of rimonabant at a clinically relevant dose. Clinical Pharmacology & Therapeutics (2005) 79, P77–P77; doi: 10.1016/j.clpt.2005.12.275