التفاصيل البيبلوغرافية
| العنوان: |
Population pharmacokinetics and Bayesian estimation of tacrolimus exposure in Chinese liver transplant patients. |
| المؤلفون: |
Chen, B., Shi, H.‐Q., Liu, X.‐X., Zhang, W.‐X., Lu, J.‐Q., Xu, B.‐M., Chen, H. |
| المصدر: |
Journal of Clinical Pharmacy & Therapeutics; Dec2017, Vol. 42 Issue 6, p679-688, 10p |
| مصطلحات موضوعية: |
TACROLIMUS, GENETIC polymorphisms, LIVER transplantation, TRANSPLANTATION of organs, tissues, etc., GENOTYPES |
| مصطلحات جغرافية: |
CHINA |
| مستخلص: |
What is known and objectives Tacrolimus ( TAC) is widely used as part of immunosuppressive regimens. There is great interindividual variation on the disposition of TAC. The aim of this study was to develop a population pharmacokinetic ( PPK) model for Chinese liver transplant patients and evaluate genetic polymorphism and other possible factors on the PK parameters. The exposure of TAC is to be estimated through Bayesian modelling. Methods A total of 47 sets of rich-time PK and 1234 conventional therapeutic drug monitoring ( TDM) data were collected from 125 Chinese liver transplant patients. The pathophysiological data of these patients were recorded. CYP3A5*3 and ABCB1 genotypes were determined for each patient. The PPK model for TAC was established by nonlinear mixed-effects modelling ( nonmem). The impact of pathophysiology and genotype on PPK parameters was evaluated. Bayesian estimators for the area under concentration-time curve ( AUC) of TAC were validated. Results A two-compartment model with lag time was found to be the most suitable model for the pooled full PK and TDM data for Chinese liver transplant patients. The CL/F, V2/F, Q/F, V3/F, Ka and lag time were 17.4±0.81 L/h, 165±44.1 L, 54.9±25.8L/h, 594±87.5 L, 0.51±0.095 L/h and 1.57±0.34 h. Post-operative day ( POD), creatinine clearance ( CLcr) and ABCB1 C3435T genotypes were found to have significant influences on CL/F ( P<.01). ABCB1 C3435T genotypes showed a significant correlation with V2/F ( P<.01). C0-C2 and C0-C2-C4 were shown to be suitable for the estimation of AUC in Chinese liver transplant patients. What is new and conclusion A PPK model for TAC was established successfully in Chinese liver transplant patients. POD, CLcr and ABCB1 C3435T genotypes were shown to have significant effects on CL/F. The AUC of TAC in Chinese liver transplant patients could be estimated through Bayesian modelling, based on which individualized immunosuppressive regimens can be designed. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
