Clinical aspects of ketoconazole administration for cyclosporine A dose reduction in kidney transplant recipients

Ketoconazole (Keto), an inhibitor of the cytochrome P-450 system, can reduce the cyclosporine (CsA) dose and the cost of treatment in renal transplant patients. In this study we evaluated possible metabolic consequences of Keto and CsA coadministration. A group of renal transplant recipients taking 100 mg/day Keto (n = 23) was compared with a control group not receiving Keto (n = 13) during three years aftertransplantation. Evaluation of all patients included graft function, liver function tests, bone status, control of CsA blood concentration, mean arterial pressure (MAP) and body weight (BW) monitoring. The initial CsA dose was 3,478 ± 0,102 mg/kg/day in the Keto group and 5,500 ± 0,196 mg/kg/day in the control, p < 0,001. CsA dose reduction was 70% at 6 months aftertransplantation in patients receiving Keto and only 26% in recipients without Keto. Graft function and frequency of rejection episodes was similar in both group. Serum bilirubin, albumin, ALT, GGTP, cholesterol, calcium, phosphorus, alkaline phosphatase, PTH and bone mineral density were no different between Keto group and No-Keto group. Fracture rate was lower in the Keto group comparing with control (0,0324 versus 0,0379 patient years). Keto did not influence negatively on MAP and BW changes. We conclude that long-term use of low dose Keto in CsA-treated renal transplant recipients is safe and cost-saving.

трансплантация почки, циклоспорин А, кетоконазол, функция трансплантата, функция печени, АД, масса тела, фосфорно-кальциевый обмен

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