Trough concentrations of cyclosporine in blood following administration with grapefruit juice
- PMID:12959294
- PMCID: PMC1364619
- DOI: 10.1111/j.1365-2125.1993.tb00395.x
Trough concentrations of cyclosporine in blood following administration with grapefruit juice
Abstract
Components of grapefruit juice have been shown to inhibit CYP3A4 activity, the enzyme involved in cyclosporine metabolism. Eleven medically stable patients (seven males, four females) receiving cyclosporine following kidney transplantation were instructed to take their usual dose of cyclosporine with water for 1 week (Phase 1), with grapefruit juice (8 ounces) for 1 week (Phase 2) and again with water for 1 week (Phase 3). Trough blood samples were obtained at the end of each phase for measurement of cyclosporine concentration using a specific monoclonal whole blood radioimmunoassay. Cyclosporine trough concentrations averaged 116.9 +/- 51.6 ng ml(-1) in the first phase, 145.3 +/- 44.7 ng ml(-1) with grapefruit juice (P < 0.05 compared with the first and third phases) and 111.2 +/- 56.1 ng ml(-1) in the third phase. Cyclosporine concentrations increased in 8 of 11 patients when given with grapefruit juice (mean increase 32%; range -4 to 97%) and declined in 10 of 11 when subjects resumed taking cyclosporine with water (mean decrease 27%). These results suggest that grapefruit juice increases trough concentrations of cyclosporine in blood, possibly by inhibiting pre-hepatic gut wall metabolism, and could be useful in optimizing therapy with this drug.
Similar articles
- 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein.Edwards DJ, Fitzsimmons ME, Schuetz EG, Yasuda K, Ducharme MP, Warbasse LH, Woster PM, Schuetz JD, Watkins P.Edwards DJ, et al.Clin Pharmacol Ther. 1999 Mar;65(3):237-44. doi: 10.1016/S0009-9236(99)70102-5.Clin Pharmacol Ther. 1999.PMID:10096255Clinical Trial.
- Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients.Min DI, Ku YM, Perry PJ, Ukah FO, Ashton K, Martin MF, Hunsicker LG.Min DI, et al.Transplantation. 1996 Jul 15;62(1):123-5. doi: 10.1097/00007890-199607150-00023.Transplantation. 1996.PMID:8693526Clinical Trial.
- Disposition of intravenous and oral cyclosporine after administration with grapefruit juice.Ducharme MP, Warbasse LH, Edwards DJ.Ducharme MP, et al.Clin Pharmacol Ther. 1995 May;57(5):485-91. doi: 10.1016/0009-9236(95)90032-2.Clin Pharmacol Ther. 1995.PMID:7768070Clinical Trial.
- Interaction of Citrus Juices with Cyclosporine: Systematic Review and Meta-Analysis.Sridharan K, Sivaramakrishnan G.Sridharan K, et al.Eur J Drug Metab Pharmacokinet. 2016 Dec;41(6):665-673. doi: 10.1007/s13318-016-0351-4.Eur J Drug Metab Pharmacokinet. 2016.PMID:27278683Review.
- Drug-grapefruit juice interactions.Kane GC, Lipsky JJ.Kane GC, et al.Mayo Clin Proc. 2000 Sep;75(9):933-42. doi: 10.4065/75.9.933.Mayo Clin Proc. 2000.PMID:10994829Review.
Cited by
- Effects of food on clinical pharmacokinetics.Singh BN.Singh BN.Clin Pharmacokinet. 1999 Sep;37(3):213-55. doi: 10.2165/00003088-199937030-00003.Clin Pharmacokinet. 1999.PMID:10511919Review.
- Grapefruit juice-drug interactions.Bailey DG, Malcolm J, Arnold O, Spence JD.Bailey DG, et al.Br J Clin Pharmacol. 1998 Aug;46(2):101-10. doi: 10.1046/j.1365-2125.1998.00764.x.Br J Clin Pharmacol. 1998.PMID:9723817Free PMC article.Review.
- Stereoselective interaction of manidipine and grapefruit juice: a new twist on an old tale.Tomlinson B, Chow MS.Tomlinson B, et al.Br J Clin Pharmacol. 2006 May;61(5):529-32. doi: 10.1111/j.1365-2125.2006.02616.x.Br J Clin Pharmacol. 2006.PMID:16669845Free PMC article.No abstract available.
- Influence of chronic ingestion of grapefruit juice on steady-state blood concentrations of cyclosporine A in renal transplant patients with stable graft function.Proppe DG, Hoch OD, McLean AJ, Visser KE.Proppe DG, et al.Br J Clin Pharmacol. 1995 Mar;39(3):337-8. doi: 10.1111/j.1365-2125.1995.tb04459.x.Br J Clin Pharmacol. 1995.PMID:7619679Free PMC article.Clinical Trial.No abstract available.
- The effect of grapefruit juice on drug disposition.Hanley MJ, Cancalon P, Widmer WW, Greenblatt DJ.Hanley MJ, et al.Expert Opin Drug Metab Toxicol. 2011 Mar;7(3):267-86. doi: 10.1517/17425255.2011.553189. Epub 2011 Jan 22.Expert Opin Drug Metab Toxicol. 2011.PMID:21254874Free PMC article.Review.
References
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources