PT  - JOURNAL ARTICLE
AU  - Ke-Hua Wu
AU  - Yi-Min Cui
AU  - Jin-Feng Guo
AU  - Ying Zhou
AU  - Suo-Di Zhai
AU  - Fu-De Cui
AU  - Wei Lu
TI  - POPULATION PHARMACOKINETICS OF CYCLOSPORINE IN CLINICAL RENAL TRANSPLANT PATIENTS
AID  - 10.1124/dmd.105.004358
DP  - 2005 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 1268--1275
VI  - 33
IP  - 9
4099  - http://dmd.aspetjournals.org/content/33/9/1268.short
4100  - http://dmd.aspetjournals.org/content/33/9/1268.full
SO  - Drug Metab Dispos2005 Sep 01; 33
AB  - Population pharmacokinetics of cyclosporine (CsA) in clinical renal transplant patients has been reported in the present study. A total of 2548 retrospective drug monitoring data points were collected from 120 renal transplant patients receiving CsA. Population modeling was performed using the 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 the influence of six significant covariates, comprising postoperative days (POD), total bilirubin level (TBIL, micromolar concentration), current body weight (CBW, kilograms), age (years), concurrent metabolic inhibitors of cyclosporine (INHI), and hematocrit (HCT, percentage), 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) (liters per hour). The values in parentheses 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 interpatient 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. The American Society for Pharmacology and Experimental Therapeutics