Population pharmacokinetics and Bayesian estimation of tacrolimus exposure in Chinese liver transplant patients.
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 g...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 42; no. 6; pp. 679 - 689 |
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| Autores principales: | , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Dec2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=126069179&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 126069179 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Dec2017 vid: 42 iid: 6 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 126069179 126069179 126069179 10.1111/jcpt.12599 126069179 ppf: 679 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Population pharmacokinetics and Bayesian estimation of tacrolimus exposure in Chinese liver transplant patients. aug: au: Chen, B. Shi, H.‐Q. Liu, X.‐X. Zhang, W.‐X. Lu, J.‐Q. Xu, B.‐M. Chen, H. affil: Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China sug: subj: Tacrolimus Pharmacokinetics Transplant Recipients Liver Transplantation China China Human Male Female Genotype Polymorphism, Genetic Male Female ab: 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. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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