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• W2080675242 abstract "To determine the effects of grapefruit juice on the pharmacokinetics of oral digoxin, a P-glycoprotein substrate not metabolized by cytochrome P450 3A4, in healthy volunteers, and to assess whether polymorphic multidrug-resistance-1 (MDR1) expression contributes to interindividual variability in digoxin disposition.Prospective, open-label, unblinded, crossover study.University research center.Seven healthy adult volunteers (four men, three women).Each subject received a single oral dose of digoxin 1.0 mg with water or grapefruit juice with at least a 2-week washout between treatments. During the grapefruit juice phase, juice was administered 3 times/day for 5 days before digoxin administration to maximize any effect on P-glycoprotein.Digoxin pharmacokinetics in the presence and absence of grapefruit juice were compared. The MDR1 exon 26 C3435T genotype was determined by real-time polymerase chain reaction. Compared with water, grapefruit juice significantly reduced the digoxin absorption rate constant (3.0 +/- 2.4 to 1.2 +/- 1.0 hr(-1), p<0.05) and increased absorption lag time (0.32 +/- 0.12 to 0.53 +/- 0.34 hr, p<0.05). Grapefruit juice did not affect digoxin maximum concentration (Cmax), area under the curve (AUC), elimination half-life, or renal clearance. The effect of grapefruit juice on digoxin Cmax (-45% to +41%) and AUC(0-4) (-29% to +25%) varied substantially among subjects and was inversely correlated with the values during the water phase. Trends toward higher digoxin Cmax AUC, and absorption rate constant during the water phase were found in CC homozygotes compared with subjects carrying a T allele.Inhibition of intestinal P-glycoprotein does not appear to play an important role in drug interactions involving grapefruit juice. Interindividual variability in response to grapefruit juice may be related to the balance of intestinal drug uptake and efflux transport." @default.
• W2080675242 created "2016-06-24" @default.
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• W2080675242 date "2003-08-01" @default.
• W2080675242 modified "2023-09-24" @default.
• W2080675242 title "Effects of Grapefruit Juice on Intestinal P-glycoprotein: Evaluation Using Digoxin in Humans" @default.
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• W2080675242 doi "https://doi.org/10.1592/phco.23.8.979.32881" @default.
• W2080675242 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12921244" @default.
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