The Effect of Orlistat on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Volunteers

Publisher Website
Google Scholar
Abstract
To assess the effect of orlistat on the pharmacokinetics and pharmacodynamics of warfarin, a third‐party blind, placebo‐controlled, randomized, two‐way crossover study was performed in 12 healthy volunteers. Each participant received single 30‐mg oral doses of racemic warfarin sodium (Coumadin; DuPont Pharma, Wilmington, DE) administered on the eleventh day of treatment with 120 mg orlistat (treatment A) and placebo (treatment B) three times a day for 16 days; the two treatments were separated by a 3‐week washout period. Serial blood samples were collected before and at appropriate intervals after each dose of warfarin to determine plasma concentrations of R‐warfarin and S‐warfarin and blood prothrombin time (PT) and plasma Factor VII concentration. In addition, serum concentrations of vitamin K1 and its epoxide and of osteocalcin and its undercarboxylated form were measured before breakfast on days −7, 1, 4, 6, and 10. Equivalent results between treatments with orlistat and placebo were found with regard to all pharmacokinetic parameters of R– and S‐warfarin (except for time to maximum concentration of R‐warfarin). Pharmacodynamic parameters of warfarin (PT and Factor VII) and vitamin K nutritional status parameters (ratios of vitamin K1 to vitamin K1 epoxide and undercarboxylated osteocalcin to osteocalcin) also were unaltered by orlistat. Orlistat administered at doses of 120 mg three times daily did not significantly alter the pharmacokinetics and pharmacodynamics of a single 30‐mg oral dose of warfarin in healthy volunteers.