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Drug Metabolism and Disposition Fast Forward
First published on June 2, 2005; DOI: 10.1124/dmd.105.004358

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Received for publication March 1, 2005.
Revised May 23, 2005.
Accepted for publication May 24, 2005.

Population Pharmacokinetics of Cyclosporine in Clinical Renal Transplant Patients

Kehua Wu 1, Yi-Min Cui 2, Jin-Feng Guo 2, Ying Zhou 2, Suo-Di Zhai 3, Fu-De Cui 4, Wei Lu 1*

1 Peking University School of Pharmacetical Science 2 Peking University First Hospital 3 Peking University Third Hospital 4 Shenyang Pharmaceutical University

* Address correspondence to: E-mail: wlu01{at}ureach.com

Abstract

Population pharmacokinetics of cyclosporine (CsA) in the clinical renal transplant patients has been reported in the present study. A total of 2, 548 retrospective drug monitoring data points were collected from 120 renal transplant patients receiving CsA. Population modeling was performed using NONMEM (nonlinear mixed-effect modeling) program, using a one-compartment model with first-order absorption and elimination. The final regression model for CsA clearance (CL/F) with influence of six significant covariates, which is comprised of post- operative days (POD), total bilirubin level (TBIL, µM), current body weight (CBW kg), age (Age, year), concurrent metabolic inhibitors of cyclosporine (INHI) and hematocrit (HCT, %), has been established and expressed as CL/F=28.5-1.24*POD-0.252*(TBIL-11)+0.188*(CBW-58) -0.191*(Age-42)-2.45*INHI-0.212*(HCT-28) (L/h). The values in parenthesis represent the median level for each of the corresponding covariates. The population estimates for CL/F (28.5 L/h), V/F (volume of distribution, 133 L) and inter-patient variability (CV% = 19.7%) for CL/F were achieved, respectively. The population model was further validated by internal and external approaches, and was demonstrated to be effective and stable. Moreover, simulation was conducted to facilitate the individualized treatment based on patient information and the final model.


Key words: pharmacokinetic modeling, pharmacokinetics


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Population-based assessments of clinical drug-drug interactions: qualitative indices or quantitative measures?
J. Clin. Pharmacol., November 1, 2006; 46(11): 1268 - 1289.
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