EFFECT OF GRAPEFRUIT JUICE ON CYCLOSPORINE PHARMACOKINETICS IN RENAL-TRANSPLANT PATIENTS

This study investigated the effect of grapefruit juice on cyclosporine A (CsA) bioavailability in 10 renal transplant patients. Under CsA st eady state conditions, patients were randomly administered their usual dose of CsA with either 8 ounces of grapefruit juice or 8 ounces of w ater, Using a crossover design, a 12-hr pharmacokinetic study was then conducted. Grapefruit juice increased the area under the concentratio n versus time curve (4218+/-1497 ng . hr/ml [grapefruit juice] vs. 341 5+/-1288 ng . hr/ml [water], P=0.029) and 12-hr trough (244+/-214 ng/m l [grapefruit juice] vs. 132+/-56 ng/ml [water], P=0.09), but it did n ot change peak concentration (734+/-290 ng/ml [grapefruit juice] vs. 7 08+/-305 ng/ml [water], P=0.76). In addition, grapefruit juice delayed the time to peak concentration compared with water (5.4+/-3.0 hr [gra pefruit juice] vs. 2.8+/-0.8 hr [water], P=0.025). These data suggest that concurrent administration of grapefruit juice with CsA will delay the absorption of CsA and increase the drug exposure of CsA without c hanging peak concentration.