A NOMOGRAM FOR PREDICTING OPTIMAL DOSAGE OF CYCLOSPORINE RENAL-TRANSPLANT PATIENTS - TAKING PHYSIOLOGICAL FACTORS INTO CONSIDERATION FOR REGIMEN DURING IMMUNOSUPPRESSIVE THERAPY

We constructed a nomogram for determining the optimal regimen of cyclo sporine (CyA), based on physiological changes that occur during immuno suppressive therapy. The nomogram consists of a fixed model and a vari able model. In the fixed model, the oral dose of CyA (D, mg/kg) is giv en 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 distr ibution ratio of CyA (CyA-EP), as defined by: D = 4.938 x log(TL)+ 1.5 037 x CL/f(su) - 0.0326 x CyA-EP - 10.7156. In the variable model, the CL/f(su) is given by the CYA-EP and the patient's intrinsic parameter s (P-1, P-2), using a nonlinear equation: CL/f(su) = P-1 x exp(P-2 x C yA-EP)/CyA-EP. An optimal CyA dose to maintain a desired trough level was calculated, and the validity of the nomogram was found satisfactor y for clinical use. This offers a very concise and practical method fo r the therapeutic monitoring of CyA. Because the pharmacokinetics of C yA depends on physiological changes due to several disease states, and because the CyA-EP reflects the pharmacokinetics of CyA and the patie nt's disease state, the proposed nomogram is believed to provide an op timal dosage adjustment, taking physiological factors into considerati on.