The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients
| Autor: | A. A. M. J. Hollander, Francis Arbouw, Adam F. Cohen, Fokko J. van der Woude, Leendert A. van Es, Joost B. van Bree, Jeroen van Rooij, Rik C. Schoemaker, Eef G.W.M. Lentjes |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Adult
Male Citrus food.ingredient medicine.drug_class Prednisolone Pharmacology Grapefruit juice Beverages Food-Drug Interactions food Pharmacokinetics Prednisone medicine Humans Pharmacology (medical) Chemistry Area under the curve food and beverages Kidney Transplantation Crossover study Transplantation Cyclosporine Corticosteroid Female medicine.drug |
| Zdroj: | Clinical Pharmacology & Therapeutics. 57:318-324 |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1016/0009-9236(95)90157-4 |
| Popis: | Objective To estimate the effect of grapefruit juice on cyclosporine and prednisone metabolism. Methods 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 metabolites/area 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 ng/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 significant 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 P450 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. Clinical Pharmacology & Therapeutics (1995) 57, 318–324; doi |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text