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Influence of grapefruit juice on cisapride pharmacokinetics
Author(s) -
Gross Annette S.,
Goh Yan D.,
Addison Russell S.,
Shenfield Gillian M.
Publication year - 1999
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(99)70133-5
Subject(s) - grapefruit juice , cisapride , pharmacokinetics , cmax , chemistry , bioavailability , citrus paradisi , urine , pharmacology , oral administration , food science , medicine , biochemistry , rutaceae , botany , biology
Objective Grapefruit juice increases the oral bioavailability of several drugs metabolized by cytochrome P450 3A4. This study investigated the influence of grapefruit juice on the pharmacokinetics of oral cisapride, a substrate of CYP3A4. Methods Fourteen healthy volunteers received in random order 10 mg cisapride (Prepulsid) with 250 mL water or grapefruit juice after an overnight fast. Blood samples were taken for 25 hours and urine was collected for 36 hours after dosing. Plasma concentrations of cisapride and urinary norcisapride were measured by HPLC. The influence of grapefruit juice on pharmacokinetic parameters (mean ± SD) was assessed with the Wilcoxon matched pairs test for 13 subjects (1 subject did not fast as instructed). Results Grapefruit juice increased cisapride maximum measured plasma concentration (C max ; water, 65 ± 398 ng/mL; grapefruit juice, 87 ± 40 ng/mL; P = .009) and area under the plasma concentration–time curve from 0 to 25 hours [AUC(0‐25); water, 418 ± 280 h · ng/mL; grapefruit juice, 580 ± 289 h · ng/mL; P = .005] and prolonged the time to reach C max (water, 1.26 ± 0.36 hours; grapefruit juice, 1.72 ± 0.55 hours; P = .02). Half‐life was not affected. Urinary norcisapride recovery was similar and thus the partial apparent metabolic clearance to norcisapride was lower ( P = .046) after grapefruit juice (89.5 ± 41.2 mL/min) than after water (121.5 ± 54.7 mL/min). There was considerable interindividual variation in the grapefruit juice effect [range of AUC(0‐25) grapefruit juice/water ratio, 0.90 to 2.65). Conclusions Grapefruit juice increases the oral bioavailability of cisapride, with large interindividual variation in the change in C max and AUC. Because cisapride has a wide therapeutic index, the interaction may not be of major clinical significance for efficacy, but further studies are necessary at steady state to rule out the possibility of side effects in susceptible individuals. Clinical Pharmacology & Therapeutics (1999) 65 , 395–401; doi: