THE INFLUENCE OF REDUCED DIETARY-FAT ABSORPTION INDUCED BY ORLISTAT ON THE PHARMACOKINETICS OF DIGOXIN IN HEALTHY-VOLUNTEERS

To assess the influence of an orlistat-induced reduction in dietary fat absorption on the pharmacokinetics of digoxin, an open-label, placebo-controlled, randomized, two-way crossover study was performed in 12 healthy volunteers. Each subject received single 0.4-mg doses of digoxin (soft gelatin capsules) administered orally on the fourth day of orlistat (120 mg three times daily for 6 days) and placebo (three times daily for 6 days) treatment, separated by at least an 11-day washout period. Serial blood samples were collected before and at appropriate intervals after each digoxin dose to determine plasma concentrations of unchanged digoxin. The 90% confidence intervals for the ratio of geometric least-squares means (for C-max,C- AUC(0-48,) AUCo(0-t,) and AUC) and for the difference of arithmetic least-squares means (for t(max) and lambda(z)) indicate that the pharmacokinetics of digoxin was not altered by treatment with orlistat. This result suggests that a similar to 30% reduction in dietary fat absorption will not change the efficacy of digoxin in cardiac patients.