Population pharmacokinetic study of cyclosporine in patients with nephrotic syndrome

Cyclosporine (CsA) is widely used in the treatment of nephrotic syndrome (NS). A population pharmacokinetic (PopPK) model was developed using trough blood CsA concentration data from 106 patients with NS. The pharmacokinetic analysis was performed using NONMEM with 1-compartment linear model and first-order elimination. Proportional and additive error models were used to describe the interindividual and intraindividual variabilities, respectively. Body weight (WT), serum albumin level (ALB), and combination therapy with rifampicin were found to be the most significant covariates explaining the variability of the apparent clearance (CL/F) of CsA among patients. The final model was as follows: TVCL/F=34.1x(WT/67.6)(1.08)x(1+RFAx0.67)x(1-ALBx0.0088); TVV/F=3.5xWT; Ka=1.28 fixed; where RFA=1 with concurrent rifampicin use and 0 otherwise. The interindividual variabilities of CL/F and V/F were 18% and 27%, respectively. The residual error was 0.064 mg/L. The mean+/-SD of CL/F and V/F of the 106 patients were 23.5+/-7.2 L/h and 232.3+/-71.5 L, respectively. The reliability and stability of the PopPK model were confirmed by nonparametric bootstrap procedure.