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Development and validation of individualized tacrolimus dosing software for Chinese pediatric liver transplantation patients: a population pharmacokinetic approach

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机构: [1]Department of Pharmacy, Beijing Friendship Hospital,Capital Medical University, 95 Yong An Road, Xi ChengDistrict, Beijing 100050, China [2]Department of Interventional Radiography, BeijingFriendship Hospital, Capital Medical University,Beijing 100050, China [3]Pharmacy Department of Beijing Health VocationalCollege, No. 128, Jiukeshu East Road, Tongzhou District,Beijing 101101, China [4]Department of Pharmacy, Peking University First Hospital,Beijing, China [5]Department of Pharmacy, Xuanwu Hospital of CapitalMedical University, Beijing 100053, China
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关键词: Individualized dosing software  Tacrolimus  Population pharmacokinetics  Liver transplantation  Chinesepediatric patients  Under 4 years old

摘要:
We aim to describe the population pharmacokinetics (PPK) of tacrolimus in Chinese pediatric patients under 4 years old after liver transplantation and to develop individualized tacrolimus dosing software.A total of 663 blood concentrations from 85 patients aged 4.57 months to 3.97 years were collected in this study. PPK analysis was performed using a nonlinear mixed effects modeling approach with the software, Phoenix. Using C#, an individualized tacrolimus dosing software was created. The software was then used to predict the concentrations of another ten pediatric liver transplantation patients to verify the accuracy of said software. The predictive error (PE) and the absolute predictive error (APE) for each predicted time point were computed.A one-compartment model with first-order elimination best fitted the data. The apparent volume of distribution (V/F) and apparent clearance (CL/F) were 198.65 L and 2.41 L/h. Postoperative days (POD), total bilirubin (TBIL), and the use of voriconazole significantly influenced tacrolimus apparent clearance. The incorporation of an increasing number of actual blood drug concentrations into the prediction resulted in a decrease in both PE (72%, 17%, 7%) and APE (87%, 53%, 26%).A qualified PPK model of tacrolimus was developed in Chinese pediatric patients. The individualized tacrolimus dosing software could be used as a suitable tool for the personalization of tacrolimus dosing for pediatric patients after liver transplantation.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 3 区 药学
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大类 | 3 区 医学
小类 | 3 区 药学
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出版当年[2022]版:
Q3 PHARMACOLOGY & PHARMACY
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Q3 PHARMACOLOGY & PHARMACY

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第一作者机构: [1]Department of Pharmacy, Beijing Friendship Hospital,Capital Medical University, 95 Yong An Road, Xi ChengDistrict, Beijing 100050, China
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