OBJECTIVES: Grapefruit juice is responsible for drug interactions mediated by intestinal cytochrome P4503A4 inhibition and possibly @entity1262 inhibition in enterocytes. Our main objective was to determine whether grapefruit juice alters the bioavailability of @entity6838 , a @entity1262 substrate. The secondary objective was to determine whether the magnitude of the pharmacokinetic interaction was influenced by @entity1262 genetic polymorphism. METHODS: Twelve healthy volunteers participated in this open randomized crossover study comparing the effect of grapefruit juice consumption (versus water) on the pharmacokinetics of a single oral dose of @entity6838 (0.5 mg). The @entity1262 genotype was determined according to @entity1262 genetic polymorphism in exon 26 ( @entity7658 ). RESULTS: Grapefruit juice had no significant effect on the maximum plasma drug concentration (C(max)) of @entity6838 or the area under the plasma concentration-time curve (AUC) from time zero to 48 hours. However, there was a 9% increase in the @entity6838 AUC from time zero to 4 hours and from time zero to 24 hours (P =.01) during grapefruit juice administration. The @entity6838 renal clearance remained unchanged during both periods. No relationship between @entity1262 @entity7658 genotype and early @entity6838 pharmacokinetic changes could be detected. CONCLUSION: The modest changes in @entity6838 pharmacokinetics observed during grapefruit juice ingestion do not support an important @entity1262 inhibition. Under our experimental conditions, grapefruit juice-mediated @entity1262 inhibition does not appear to play a relevant role in drug interactions, at least when assessed by use of @entity6838 disposition kinetics.

Effect of grapefruit juice on XXXX pharmacokinetics in humans.

@entity6838 :: ('MESH:D004077', 'Chemical') :: ['digoxin'] @entity1262 :: ('5243', 'Gene') :: ['P-glycoprotein', 'MDR1'] @entity7658 :: ('c|SUB|C|3435|T', 'DNAMutation') :: ['C3435T']
@entity6838 :: (MESH:D004077,Chemical) :: ['digoxin']
