Interaction Between Cyclosporine and Grapefruit Juice Requires Long‐Term Ingestion in Stable Renal Transplant Recipients

STUDY OBJECTIVE: To examine the effect of the concurrent administration of increasing amounts of grapefruit juice, an inhibitor of drug metabolism, on the steady-state pharmacokinetics of cyclosporine. DESIGN: Open-label, three-period crossover, food-drug interaction study in stable renal transplant patients. SETTING: A university-affiliated clinical research center. PATIENTS: Sixteen stable renal transplant recipients. INTERVENTION: Cyclosporine was administered with 240 ml of water, 240 ml of grapefruit juice, or several 240-ml glasses of grapefruit juice, and serial blood samples were taken to estimate the effect of grapefruit juice on cyclosporine pharmacokinetics. MEASUREMENTS AND MAIN RESULTS: Grapefruit juice caused a significant increase in cyclosporine area under the curve, however, no significant effect was seen in other pharmacokinetic parameters. Grapefruit juice caused an increase in the 24-hour trough cyclosporine concentration, which may be of clinical significance if long-term ingestion of grapefruit juice is recommended. CONCLUSION: A drug interaction exists between cyclosporine and grapefruit juice, and it is likely at the level of intestinal drug absorption.