A Nomogram for Predicting Optimal Dosage of Cyclosporine in Renal Transplant Patients : Taking Physiological Factors into Consideration for Regimen during Immunosuppressive Therapy

概要

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We constructed a nomogram for determining the optimal regimen of cyclosporine (CyA), based on physiological changes that occur during immunosuppressive therapy. The nomogram consists of a fixed model and a variable model. In the fixed model, the oral dose of CyA (D, mg/kg) is given by the multiple linear function of logarithmic CyA trough level (TL, ng/ml), the surrogate apparent total body clearance of CyA (CL/f_<su>, 1/h/kg, being equal to D/TL/12), and the erythrocyte-to-plasma distribution ratio of CyA (CyA-EP), as defined by : D=4.938×log (TL)+1.5037×CL/f_<su>-0.0326×CyA-EP-10.7156. In the variable model, the CL/f_<su> is given by the CyA-EP and the patient's intrinsic parameters (P_1,P_2), using a nonlinear equation : CL/f_<su>=P_1×exp (P_2×CyA-EP)/CyA-EP. An optimal CyA dose to maintain a desired trough level was calculated, and the validity of the nomogram was found satisfactory for clinical use. This offers a very concise and practical method for the therapeutic monitoring of CyA. Because the pharmacokinetics of CyA depends on physiological changes due to several disease states, and because the CyA-EP reflects the pharmacokinetics of CyA and the patient's disease state, the proposed nomogram is believed to provide an optimal dosage adjustment, taking physiological factors into consideration.
公益社団法人日本薬学会の論文
1995-10-15