Population pharmacokinetics of cyclosporine A in Chinese patients with nephrotic syndrome in individualized drug administration .

OBJECTIVE To establish a population pharmacokinetic (PopPK) model of cyclosporine A (CsA) in Chinese patients with nephrotic syndrome (NS) and to use the model to guide the adjustment of individualized dosage regimens. MATERIALS AND METHODS 216 CsA therapeutic drug monitoring (TDM) concentration observations were collected from 127 Chinese patients with NS. The basic model was developed as a one-compartment PK model with first-order absorption and linear elimination. The first-order conditional estimation (FOCE) method was applied to establish the final model with covariates using NONMEM software. The final model was evaluated through internal validation including goodness-of-fit analysis and bootstrap method as well as external validation using 39 additional PK observations from 35 patients with NS. RESULTS A PopPK model of CsA was established in Chinese NS patients with influence of body weight on clearance. The internal and external validation results showed that the final model was stable. CONCLUSION The established population model adequately characterized the PK of CsA in Chinese patients and could support individualized medication during treatment of NS with CsA.
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