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Tytuł:
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Impact of Donor and Recipient CYP3A5*3 Genotype on Tacrolimus Population Pharmacokinetics in Chinese Adult Liver Transplant Recipients.
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Autorzy:
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Shao J; Tianjin First Central Hospital, Tianjin, China.
Wang C; Huashan Hospital, Fudan University, Shanghai, China.
Fu P; Tianjin First Central Hospital, Tianjin, China.
Chen F; Tianjin First Central Hospital, Tianjin, China.
Zhang Y; Tianjin First Central Hospital, Tianjin, China.
Wei J; Tianjin University of Traditional Chinese Medicine, Tianjin, China.
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Źródło:
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The Annals of pharmacotherapy [Ann Pharmacother] 2020 Jul; Vol. 54 (7), pp. 652-661. Date of Electronic Publication: 2019 Dec 30.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Sept. 2013- : Thousand Oaks, CA : Sage
Original Publication: Cincinnati, OH : Harvey Whitney Books Co., c1992-
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MeSH Terms:
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Liver Transplantation*
Models, Biological*
Polymorphism, Genetic*
Cytochrome P-450 CYP3A/*genetics
Immunosuppressive Agents/*pharmacokinetics
Tacrolimus/*pharmacokinetics
Adult ; Asian People ; Drug Monitoring ; Female ; Genotype ; Humans ; Immunosuppressive Agents/administration & dosage ; Male ; Metabolic Clearance Rate ; Middle Aged ; Tacrolimus/administration & dosage ; Tissue Donors ; Transplant Recipients
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Contributed Indexing:
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Keywords: CYP3A5*3; liver transplantation; population pharmacokinetics; tacrolimus
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Substance Nomenclature:
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0 (Immunosuppressive Agents)
EC 1.14.14.1 (CYP3A5 protein, human)
EC 1.14.14.1 (Cytochrome P-450 CYP3A)
WM0HAQ4WNM (Tacrolimus)
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Entry Date(s):
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Date Created: 20200101 Date Completed: 20201030 Latest Revision: 20221207
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Update Code:
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20240104
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DOI:
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10.1177/1060028019897050
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PMID:
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31888346
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Background: Tacrolimus (TAC) is widely used after liver transplantation, but the therapeutic window is narrow. Objective: The purpose was to study both donor and recipient CYP3A5*3 genotypes affecting TAC apparent clearance rate (CL/F) and investigate a TAC population pharmacokinetic (PPK) model in Chinese liver transplant recipients for potential starting-dose individualized medication. Methods: A data set of 721 TAC concentrations was obtained from 43 adult liver transplant recipients. The TAC PPK model was analyzed using nonlinear mixed-effects modeling. Potential covariates, including demographic characteristics, physiological and pathological data, concomitant medications, and CYP3A5*3 genotype, were evaluated. The final model was validated using normalized prediction distribution errors and bootstrapping. Results: A 2-compartment model with first-order absorption and elimination was used to describe TAC disposition. Population estimates of TAC, CL/F, apparent central distribution volume (V2/F), rate of absorption (K a ), and apparent peripheral distribution volume (V 3 /F) were 18.1 L/h (12%), 72.7 L (34%), 0.163 h -1 (17%), and 412 L (21%), respectively. The model and estimated parameters were found to be stable. Other covariates did not influence TAC CL/F. Both donor and recipient CYP3A5*1 genotypes were significantly correlated with TAC clearance, and CL/F was 1.70-fold higher in both donor and recipient CYP3A5*1 carriers than in noncarriers among Chinese liver transplant recipients. Conclusion and Relevance: A PPK model of TAC was established in Chinese adult liver transplantation recipients for starting-dose individualized medication, which can be expanded to optimize clinical efficacy and minimize toxicity with therapeutic drug monitoring.