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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Influence of grapefruit juice on cisapride pharmacokinetics.

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 (Cmax; 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 x ng/mL; grapefruit juice, 580+/-289 h x ng/mL; P = .005] and prolonged the time to reach Cmax (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 Cmax 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.[1]

References

  1. Influence of grapefruit juice on cisapride pharmacokinetics. Gross, A.S., Goh, Y.D., Addison, R.S., Shenfield, G.M. Clin. Pharmacol. Ther. (1999) [Pubmed]
 
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