Clinical observations of metabolic changes occurring in renal transplant recipients receiving ketoconazole

Transplantation
L W MooreA O Gaber

Abstract

Metabolism of cyclosporine is reduced by ketoconazole binding to the monooxygenase responsible for cyclosporine degradation. This isozyme of cytochrome P450, along with other similar monooxygenases, is involved in the regulation of the synthesis and degradation of important metabolic pathways of cholesterol. Monooxygenases throughout these pathways are inhibited by ketoconazole binding causing a decreased metabolism of calcitriol, bile acids, and steroid hormones, and can thereby potentiate altered lipid metabolism, bone metabolism, and weight status of transplant recipients. A group of renal transplant recipients taking ketoconazole (n=25) was compared with a matched cohort not receiving ketoconazole for metabolic changes during the first six months posttransplantation. Lower LDL cholesterol levels were seen in the ketoconazole group (109 +/- 8 mg/dl) than the no ketoconazole group (140 +/- 8 mg/dl) at one month but this difference was not sustained at six months. More bone loss occurred in the ketoconazole group as demonstrated by significant changes in bone density as well as a greater urinary appearance of bone collagen crosslink, deoxy-pyridinoline (29 +/- 4 nmol dpd/mmol creatinine and 18 +/- 4 at six months for the ketoc...Continue Reading

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Citations

Jun 24, 1998·Transplantation Proceedings·G HurstA Gaber
Aug 5, 1998·Current Opinion in Nephrology and Hypertension·I R Dissanayake, S Epstein
Sep 26, 2002·Psychosomatics·Scott C ArmstrongElisabeth A Pimentel
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Nov 15, 2005·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Scott R PenzakJoseph Kovacs
Jul 2, 1999·Pediatric Transplantation·S ImaniR Steiner

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