Retrospective Pharmacokinetic Data Analysis of Cyclosporin A Using Routine Monitoring Data in Renal Transplant Patients : Consideration on Its Pharmacokinetic Profiles and Physiological Factors during Renal Dysfunction

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University of Medical Science Using clinical monitoring data of cyclosporin A (CyA) from renal transplant patients at different disease phases, we examined the relationships between their CyA pharmacokinetic profiles and physiological factors. The concentration of CyA in whole blood was measured by high-performance liquid chromatography (HPLC). The pharmacokinetic parameters of CyA estimated using a zero order absorption one-compartment model at different phases of therapy showed great between- and within-individual Variations. The zero order absorption rate constant (k^0) and the area under the blood concentration-time curve (AUC_<0-12>) during acute tubular necrosis (ATN), and after an episode of nephrotoxicity or graft rejection decreased markedly, whereas the volumes of distribution (Vd) at those times increased. In a correlation study, positive intercorrelations existed between hematocrit (HCT), k^0/Vd (normalized by the Vd) and creatinine clearance (Cl_<cr>), suggesting that the change in renal function affects the absorption process of CyA, and that HCT is likely to becone an indicator for predicting CyA disposition. In this study, we discuss the clinical necessity of CyA whole blood level monitoring in consideration of the changes in physiological factors due to renal dysfunction.
日本医療薬学会の論文
1993-08-20