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Abstract
Since the introduction of cyclosporine, there has been a significant mprovement in the results of solid organ transplantation resulting in mprovement in patient and graft survival. However the deletenous effects 01 yclosporine especially nephrotoxicity and high initial cost stand as a major disadvantage for long term use of the drug. Metabolism of cyclosporine occurres almost exclusively in the liver via hepatic cytochrome P-450 microsomal enzymes. Ketoconazole which is a broad spectrum antifungal drug, has been shown to inhibit the cytochrome P¬450 enzyme system resulting in marked elevation in blood level 01 cyclosporine when both drugs are administered concomitantly. The isozyme of cytochrome. P-450, responsible for cyclosporine degradation, is also involved along with other similar monooxygenasis in the regulation of synthesis and degradation 01 important metabolic pathways of cholesterol. These monooxygenases are inhibited by ketoconazole binding causing decreased metabolism of vitamin D, bile acids and steroid hormones and can Ihereby potentiate altered lipid metabolism and bone metabolism of transplant recipients. Additionally, ketoconazole has been shown to have steroidogenic properties by other mechanisms. The objective of this work was long-term evaluation of the patient and graft outcome after 54 months of initiation of ketoconazole administration to cyclosporine treated kidney transplant recipients in addition to evaluation of the metabolic consequences of ketoconazole administration as an adjunct to cyclosporine immunosuppressive regimens. The material of this work comprised 100 living related donor kidney . transplant recipients who were previously assigned by Sobh and co-workers, 1995, in their trial to study potential safety and financial benefits of concomitant cyclosporine and ketoconazole administration for 12 months.