Abstract
Although calcium channel blockers have been reported to increase trough cyclosporine (CsA) blood levels, few studies have systematically examined the effects of calcium channel blockers on CsA pharmacokinetics. In the present investigation, complete pharmacokinetic profiles of CsA and its major metabolites (M1, M17, and M21) were determined in 11 verapamil-treated patients, 7 nifedipine-treated patients, and in 78 controls. Whole blood and urine levels were analyzed using high-performance liquid chromatography. Verapamil caused a 45% increase in CsA area under the curve, maximum concentration, steady-state concentration, and trough level. Metabolite 17 levels were increased in a parallel fashion, suggesting that altered CsA bioavailability rather than decreased metabolism may have caused the higher CsA levels in verapamil-treated patients. However, verapamil-induced reductions in CsA metabolism by other routes could not be ruled out. No changes in CsA or its metabolites were observed in nifedipine-treated patients. Unlike previous reports in patients treated with higher CsA doses, verapamil and nifedipine did not improve renal function in the present study. Nevertheless, the increase in CsA blood levels seen with verapamil may enhance the therapeutic cost-effectiveness of this agent in hypertensive renal transplant recipients.
Published Version
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