The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients

✍ Scribed by Hollander, Adrianus A. M. J.; van Rooij, Jeroen; Lentjes, Eef G. W. M.; Arbouw, Francis; van Bree, Joost B.; Schoemaker, Rik C.; van Es, Leendert A.; van der Woude, Fokko J.; Cohen, Adam F.

• Publisher: Nature Publishing Group
• Year: 1995
• Tongue: English
• Weight: 635 KB
• Volume: 57
• Category: Article
• ISSN: 0009-9236
• DOI: 10.1016/0009-9236(95)90157-4

✦ Synopsis

Objeetitw: To estimate the effect of grapefruit juice on cyclosporine and prednisone metabolism. Metboak This was an open, placebo-controlled, two-way crossover study performed in the academic departments of clinical pharmacology and nephrology. On two study occasions, 12 kidney transplant patients with stable cyclosporine trough levels received either grapefruit juice or water every 3 hours for a period of 30 hours. The main outcome measures were peak concentration and time to peak, area under the concentration-time curve, the ratio of the area under the curve of the metaboliteskea under the curve of the parent drug, terminal half-life, and 24-hour trough levels of cyclosporine. Results: Grapefruit juice increased the peak concentration of cyclosporine by 185 @ml (95% confidence interval, 60 to 310; p = 0.008). The ratio of the area under the curve of the metabolites of cyclosporine to the area under the curve of cyclosporine was reduced by 0.137 on the grapefruit day (95% confidence interval, -0.221 to -0.054;p = 0.004). After grapefruit juice, no sign&ant changes were observed in the area under the curve and the time to peak of cyclosporine, prednisone, and prednisolone. Cyclosporine trough levels were unchanged by grapefruit juice. Conclusions: Grapefruit juice inhibits the metabolism of cyclosporine for a brief period after administration, which may be explained by the inhibition of cytochrome I?450 enzymes in the gut wall and to a lesser extent by inhibition of these enzymes in the liver. Grapefruit juice can be one of the factors leading to intraindividual variability in the pharmacokinetics of cyclosporine. Grapefruit juice had no significant effect on the metabolism of prednisone or prednisolone. (