Effects of Rifampin on Cyclosporine Disposition in Kidney Recipients with Tuberculosis

신장이식 환자에서 Rifampin과 Cyclosporine의 약동학적 상호작용

Background: We present a case whose plasma cyclosporine concentrations were markedly decreased after adding antituberculosis medications. To assess the effect of rifampin on this pharmacokinetic interaction, we evaluated the pharmacokinetic changes of cyclosporine in kidney-transplanted patients with tuberculosis before and after withdrawing rifampin. Methods : Two separate full pharmacokinetic studies of cyclosporine were performed in four kidney recipients with tuberculosis before and one month after withdrawing rifampin from antituberculosis medications. Multiple blood samples were repeatedly drawn after morning oral dose of cyclosporine, and cyclosporine concentrations were determined by HPLC method. Pharmacokinetic parameters were estimated from noncompartmental method using $WinNonlin{\circledR}$ Results : After withdrawing rifampin, changing patterns of all pharmacokinetic parameters were consistent in all 4 subjects. Corrected Cmax and AUC estimated on the same 100mg dose basis were significantly increased from $291.1{\pm}54.1$ ng/ml to $950.7{\pm}174.7$ ng/ml and from $1483.1{\pm}92.0$ ng/ml ${\cdot}$ h to $6047.2{\pm}666.6$ ng /ml ${\cdot}$ hr, respectively (p($19.8{\pm}3.5$ L/kg) was decreased to $6.0{\pm}0.9$ L/kg after withdrawing rifampin. However, the prolongation of halflife was not statistically significant $(6.1{\pm}1.7 hour vs)$ $10.6{\pm}1.1)$. Conclusions : These results strongly suggest that rifampin markedly decrease the plasma concentration of cyclosporine coadministered through pharmacokinetic interaction, and careful dose readjustment should be considered from frequent monitoring of plasma cyclosporine concentrations in patients taking both cyclosporine and antituberculosis medications including rifampin.