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首都医科大学附属北京友谊医院
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.
第一作者单位:[1]Tianjin Med Univ, Basic Med Coll, Tianjin, Peoples R China
通讯作者:
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
推荐引用方式(GB/T 7714):
Yang Jian-wei,Liao Sha-sha,Zhu Li-qin,et al.Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation[J].INTERNATIONAL JOURNAL of CLINICAL PHARMACOLOGY and THERAPEUTICS.2015,53(1):75-83.doi:10.5414/CP202189.
APA:
Yang, Jian-wei,Liao, Sha-sha,Zhu, Li-qin,Zhao, Yang,Zhang, Yuan...&Sun, Li-ying.(2015).Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation.INTERNATIONAL JOURNAL of CLINICAL PHARMACOLOGY and THERAPEUTICS,53,(1)
MLA:
Yang, Jian-wei,et al."Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation".INTERNATIONAL JOURNAL of CLINICAL PHARMACOLOGY and THERAPEUTICS 53..1(2015):75-83