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.
Hoffmann-La Roche Inc., Nutley, New Jersey 07110-1199, USA.
A T
AT
Melia
J
J
Zhi
S G
SG
Koss-Twardy
B H
BH
Min
B L
BL
Smith
N L
NL
Freundlich
S
S
Arora
S M
SM
Passe
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000378:metabolism*; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007408:Intestinal Absorption; D007783:Lactones / Q000494:pharmacology*; D008049:Lipase / Q000037:antagonists & inhibitors*; D008297:Male; D000077403:Orlistat
D004041:Dietary Fats; D004791:Enzyme Inhibitors; D007783:Lactones; D004077:Digoxin; D000077403:Orlistat; D008049:Lipase