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Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation

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单位: [1]Tianjin Med Univ, Basic Med Coll, Tianjin, Peoples R China [2]Tianjin First Cent Hosp, Dept Pharm, Tianjin 300192, Peoples R China [3]China Food & Drug Adm, Beijing, Peoples R China [4]Tianjin First Cent Hosp, Dept Liver Transplantat, Tianjin 300192, Peoples R China [5]Capital Med Univ, Beijing Friendship Hosp, Dept Liver Transplantat, Beijing, Peoples R China
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关键词: tacrolimus population pharmacokinetics NONMEM Chinese pediatrics liver transplantation

摘要:
Objective: The purpose of this study was to describe the population pharmacokinetics (PK) of tacrolimus (TAC) in 52 Chinese pediatric patients early after liver transplantation. Methods: Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data from the first day after surgery. A total of 488 concentration data were obtained and analyzed by a nonlinear mixed-effect modeling (NONMEM) method. A number of demographic and clinical variables were tested for their influence on TAC PK parameters. Results: The PK of TAC were best described by a one-compartment model with first-order absorption and elimination. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 5.72 L/h and 131 L, respectively. The absorption rate constant (Ka) was fixed in 4.48 h(-1). The inter-individual variabilities in CL/F and V/F were 13.5% and 78.1%. In the final. analysis performed in all 52 patients, the post-operation day (POD) and alanine aminotransferase (ALT) influenced TAC CL/F and V/F, and total protein (TP) was the only covariate retained on V/F. Conclusion: A population PK model of TAC was developed in Chinese pediatric patients early after liver transplantation. It identified significant relationships between the PK of TAC and the characteristics of the patients. POD, ALT, and TP were identified as the main factors influencing the PK of TAC. The developed model could be useful to optimize individual pediatric TAC dosing regimen in routine clinical practice.

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出版当年[2014]版:
大类 | 4 区 医学
小类 | 4 区 药学
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 药学
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出版当年[2013]版:
Q4 PHARMACOLOGY & PHARMACY
最新[2023]版:
Q4 PHARMACOLOGY & PHARMACY

影响因子: 最新[2023版] 最新五年平均[2021-2025] 出版当年[2013版] 出版当年五年平均[2009-2013] 出版前一年[2012版] 出版后一年[2014版]

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第一作者单位: [1]Tianjin Med Univ, Basic Med Coll, Tianjin, Peoples R China
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通讯机构: [2]Tianjin First Cent Hosp, Dept Pharm, Tianjin 300192, Peoples R China [*1]Tianjin First Cent Hosp, Dept Pharm, 24 Fukang Rd, Tianjin 300192, Peoples R China
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