肾移植病人应用环孢菌素A群体药物动力学研究的临床应用

Population pharmacokinetics of Cyclosporine and its clinical application

A population pharmacokinetic model of cyclosporine (CsA) for clinical renal transplant patients was constructed to adjust CsA’s administration individually. A total of 2,548 retrospective drug monitoring data were collected from 120 Chinese renal transplant patients receiving CsA. Population modeling was performed with NONMEM by a one-compartment model with first-order absorption and elimination. Six significant covariates were included in the final model. It is postoperative days (POD), total bilirubin level (TBIL), current body weight (CBW), age, concurrent metabolic inhibitors of CsA (INHI), and hematocrit (HCT). The population means 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 estimated. The model was further validated internally and externally, and was demonstrated to be effective and robust. Moreover, in order to put the result of population pharmacokinetic studies into clinical practice, a database with the name of C-TDM for post renal transplantation patients based on the population model was established. Up on the availability of the information from clinic, the precision of the plasma concentration predicted with C-TDM was classified into 3 levels, they are population, sub-population and individual. C-TDM’s interface is user-friend, and the median value, the 90% confidence interval are simulated accompanied with comprehensive graphs, to facilitate the individualized application of CsA.

A population pharmaeokinetic model of eyelosporine （CsA） for clinical renal transplant patients was constructed to adjust CsA＇ s administration individually. A total of 2, 548 retrospective drug monitoring data were collected from 120 Chinese renal transplant patients receiving CsA. Population modeling was performed with NONMEM by a one-compartment model with first-order absorption and elimination. Six significant eovariates were included in the final model. It is postoperative days （POD）, total bilirubin level （TBIL）, current body weight （CBW）, age, concurrent metabolic inhibitors of CsA （INHI）, and hematocrit （HCT）. The population means for CL/F （28.5 L/h）, V/F （volume of distribution, 133 L）, and inter-patient vari-Fability （CV% = 19.7%） for CL/F were estimated. The model was further validated internally and externally, and was demonstrated to be effeetive and robust. Moreover, in order to put the result of population pharmaeokinetie studies into elinical praetiee, a database with the name of C- TDM for post renal transplantation patients based on the population model was established. Up on the availability of the information from elinic, the precision of the plasma concentration predieted with C-TDM was elassified into 3 levels,