Grapefruit Juice Interaction with Cyclosporine in Bone Marrow Transplantation

Recently Grapefruit juice is known to enhance the bioavailability of several clinically important drugs such as nifedipine, terfenadine, cyclosporine, ethinylestradiole, midazolam, and triazolam. Cyclosporine is an immunosuppressive agent that used in transplantation for preventation of chronic rejection. Grapefruit increase in Cmax and AUC of drug mediated by suppression of Cyp3A4 in small intestine wall.

This study has been performed by twenty Allogenic bone marrow transplant recipients at shariati hospital in Tehran. Subjects were coadministration oral cyclosporine and grapefruit juice and water as a placebo, simultaneously and two hours later.
Blood samples were collected at 3.5 and 11.5 hours following drug administrations.Blood concentration analyzed by specific monoclonal radiomimmunoassay (RIA) technique.

Grapefruit juice has significantly increase, about %42 in cyclosporin Cmax (3.5h), compared with placebo, (p=0.001). However the blood level obtained at (11.5h) Cmin was only increased about %20, (p=0.316). The average systolic and diastolic blood pressure, decreased significantly in grapefruit juice group compared with placebo, respectively (p=0.001, p=0.012).

This study demonstrated that administration of grapefruit juice had increased the cyclosporin Cmax (%42) at Iranian bone marrow transplant recipients.
Because grapefruit juice may be a safe and effective instrument to enhance absorption of many therapeutic agents, it is an appropriate means in terms of reducing dosing requirements of many Cyp3A4 substrates such as cyclosporin.