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Tacrolimus (FK506) is a macrolide drugs, clinically used for the prevention and treatment of organ rejection in transplant patients. FK506 therapeutic window is narrow, the pharmacokinetic parameter differences between individual and individual, and often require blood concentration monitoring. The purpose of this study is to investigate the population pharmacokinetic characteristics of the drug in liver transplant patients. Population pharmacokinetic studies of the drug can fully reflect the individual process differences therapy in different groups of patients, this is to develop a reasonable treatment options for the different groups to provide a reliable basis for therapy. NONMEM (nonlinear mixed effect model) method currently used for the analysis of population pharmacokinetic parameters NONMEM method advantages for cases more, but less per patient blood points, suitable for the study of population pharmacokinetic model simultaneously NONMEM individual patient pharmacokinetic parameters can be estimated subroutine POSTHOC software, so you can develop a reasonable individualized dosing regimens. Established FK506 population pharmacokinetic database, write a program to generate the data file for the the NONMEM program analysis use. Collected from the First People's Hospital, Shanghai Changzheng Hospital, 67 patients taking FK506 in liver transplant patients with cases, accurate records of its physiology, pathology and drug use, and collected blood samples from 702 steady-state trough concentration, blood IMx method concentration was determined on the results the NONMEM method of data analysis, and study the patient's age, sex, weight, daily dose and merge with other drugs such as the kinetic parameters of the drug pharmacokinetic parameters between the impact of the individual patient, the individual drug differences screened to establish the FK506 groups pharmacokinetic model affect the pharmacokinetic parameters of fixed effects, in addition to the 26 cases the data used for the model validation. Merged in determining the stability and effectiveness of the model fitting, FK506 final population pharmacokinetic parameters. The data were analyzed using a one-compartment open model and an absorption and elimination of pharmacokinetic models, and in accordance with the literature value of fixed apparent volume of distribution, absorption rate constant and bioavailability constant final fitting model: CL = 2.37 · Dose 0.542 · WT 0.732 · Age · 1.23 MYC · 1.67 LAM · 1.46 INS the formula meaning of each parameter are as follows: CL: clearance rate (unit: L · hr -1 ) Dose is: daily dosage (unit: mg / kg) the WT: weight (unit: kg) of older at the age of 45, Age = 0.836; aged between 4 to 10 years old, Age = 1.49; remaining cases Age = 1 combination of mycophenolate mofetil, MYC = 1, otherwise MYC = 0 in combination with lamivudine, LAM = Otherwise, of LAM = 0 combination of insulin, INS = 1, otherwise INS = 0 studies have shown that, with increasing body weight and dose of FK506 CL combined mycophenolate mofetil, lamivudine and insulin affect of FK506 CL . In addition, sex, combined gliquidone did not affect the clearance rate of FK506. The model results also show that: the model of inter-individual variation coefficient of 15%, and the standard deviation of the residuals 0.829μg/ml. Another group of 26 liver transplant patients data external validation of the model, the results show: the final model compared with the simplest model does not contain any explanatory variables significantly improved. The mean and variance of the standard error of prediction is close to 0 and 1, respectively, show that the model is stable and effective. According to the dose of the patient's body weight, age and concomitant medication situation, groups pharmacokinetic model used in this study can be estimated FK506 clearance rate and the recommended dose, formulate individualized dosing regimens for clinical improve efficacy and reduce drug side effects to provide the basis.
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