Scientific publications

Clinical relevance of sirolimus drug interactions in transplant patients

Sádaba B [SP], Campanero MA, Quetglas EG, Azanza JR [SP].
Department of Clinical Pharmacology, University Clinic of Navarra, Pamplona, Spain.

Magazine: Transplantic Proceedings

Date: Dec 1, 2004

Clinical Research Unit [SP] Clinical Pharmacology [SP]

ABSTRACT

Sirolimus, a new immunosuppressant drug; is metabolized by cytochrome P450 3A4 (CYP3A4) and is a substrate of the P-glycoprotein drug efflux pump. The CYP3A4/P-glycoprotein system is mainly localized in the liver and intestine. It is responsible for the severe first pass metabolism of sirolimus with a low bioavailability.

Drugs like voriconazole, itraconazole, fluconazole, and erytrhomycin may decrease the metabolic activity of this enzymatic system. This report documents in five patients that coadministration of these antimicrobials with sirolimus increases the blood concentrations of the immunosuppressant.

The dose-normalized trough blood concentration showed a mean increase of sevenfold with the coadministration of these drugs. It is essential to monitor the blood sirolimus concentrations and to adjust the sirolimus doses before and after coadministration of these drugs.

CITATION  Transplant Proc. 2004 Dec;36(10):3226-8

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