PMID: 9188374Sep 1, 1996Paper

Considerations for using ketoconazole in solid organ transplant recipients receiving cyclosporine immunosuppression

Journal of Transplant Coordination : Official Publication of the North American Transplant Coordinators Organization (NATCO)
S A ChapmanM A Kamps

Abstract

Drug interactions involving cyclosporine following transplantation are a challenging issue for the transplant clinician. This is especially true when ketoconazole is the second agent used in conjunction with cyclosporine. Because both agents are metabolized by the cytochrome P-450 IIIA4 enzyme system, cyclosporine levels rise dramatically in the presence of ketoconazole. Many other agents interact with ketoconazole, either by competitive enzyme inhibition in the liver and gastrointestinal tract, or by reducing the absorption of ketoconazole by agents that increase the pH of the gastrointestinal tract. Despite the potential cost savings when using ketoconazole to reduce cyclosporine doses, adverse effects associated with ketoconazole put patients at risk when using this combination. Close monitoring of cyclosporine levels is imperative when adding ketoconazole to cyclosporine, and once the dosage adjustments are complete, the addition of a third drug that interacts with either cyclosporine or ketoconazole could result in an unexpected rejection episode or toxic cyclosporine side effect.

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Citations

Apr 13, 2018·Parasitology·Galina I LepeshevaMichael R Waterman
Feb 12, 2020·Bioorganic & Medicinal Chemistry·Eric R Samuels, Irina F Sevrioukova

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