Impact of Donor and Recipient CYP3A5*3 Genotype on Tacrolimus Population Pharmacokinetics in Chinese Adult Liver Transplant Recipients
| العنوان: | Impact of Donor and Recipient CYP3A5*3 Genotype on Tacrolimus Population Pharmacokinetics in Chinese Adult Liver Transplant Recipients |
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| المؤلفون: | Jin-Xia Wei, Peng Fu, Jia Shao, Chenyu Wang, Yi Zhang, Fan Chen |
| المصدر: | Annals of Pharmacotherapy. 54:652-661 |
| بيانات النشر: | SAGE Publications, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Therapeutic window, medicine.medical_specialty, business.industry, medicine.medical_treatment, Population pharmacokinetics, Liver transplantation, 030226 pharmacology & pharmacy, Gastroenterology, Tacrolimus, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Genotype, medicine, Pharmacology (medical), Adult liver, CYP3A5, business |
| الوصف: | 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 (Ka), and apparent peripheral distribution volume (V3/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. |
| تدمد: | 1542-6270 1060-0280 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::5f4f08e0143a1273b1bc0c64008779b8 https://doi.org/10.1177/1060028019897050 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........5f4f08e0143a1273b1bc0c64008779b8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15426270 10600280 |
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