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 Cmax, AUC0-48, AUC0-t, and AUC) and for the difference of arithmetic least-squares means (for tmax and lambda z) indicate that the pharmacokinetics of digoxin was not altered by treatment with orlistat. This results suggests that a approximately 30% reduction in dietary fat absorption will not change the efficacy of digoxin in cardiac patients.

The influence of orlistat on the pharmacokinetics and pharmacodynamics of glyburide in healthy volunteers.

To assess the influence of orlistat on the pharmacokinetics and pharmacodynamics (the blood glucose-lowering effect) of glyburide, an open-label, placebo-controlled, randomized, two-way crossover study was done in 12 healthy male volunteers. Each subject received single 5-mg oral doses of glyburide (Micronase; The Upjohn Company, Kalamazoo, MI) on the fifth day of treatment with placebo (treatment A) and 80-mg orlistat (treatment B) three times a day for 4 1/3 days; the two treatments were separated by a five-day washout period. Serial blood samples were collected before and at appropriate intervals after each glyburide dose to determine plasma concentrations and blood glucose levels. Values of Cmax and AUC of glyburide showed an equality of the two treatments by the analysis of variance. There was an apparent correlation between blood glucose level and the logarithm of plasma glyburide concentration; this relationship appeared to not be altered when glyburide was administered with orlistat. In conclusion, orlistat administered at doses of 80-mg three times daily does not significantly alter the pharmacokinetics and blood glucose-lowering effect of a single 5-mg oral dose of glyburide in healthy volunteers.