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A population pharmacokinetic study of tacrolimus in healthy Chinese volunteers and liver transplant patients
Lu, Yan-xia1,2,3; Su, Qing-hong2,3; Wu, Ke-hua2,3; Ren, Yu-peng2,3; Li, Liang2,3; Zhou, Tian-yan2,3; Lu, Wei2,3
关键词liver transplantation healthy volunteer immunosuppressant tacrolimus population pharmacokinetics serum alanine aminotransferase
刊名ACTA PHARMACOLOGICA SINICA
2015-02-01
DOI10.1038/aps.2014.110
36期:2页:281-288
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]Chemistry ; Pharmacology & Pharmacy
关键词[WOS]PROTEIN-BINDING ; HUMAN BLOOD ; RECIPIENTS ; FK506 ; IMMUNOSUPPRESSION ; PHARMACOGENETICS ; EVOLUTION ; FK-506 ; DRUGS
英文摘要

Aim: To develop a population pharmacokinetic (PopPK) model of tacrolimus in healthy Chinese volunteers and liver transplant recipients for investigating the difference between the populations, and for potential individualized medication.

Methods: A set of 1100 sparse trough concentration data points from 112 orthotopic liver transplant recipients, as well as 851 dense data points from 40 healthy volunteers receiving a single dose of tacrolimus (2 mg, po) were collected. PopPK model of tacrolimus was constructed using the program NONMEM. Related covariates such as age, hepatic and renal functions that were potentially associated with tacrolimus disposition were evaluated. The final model was validated using bootstrapping and a visual predictive check.

Results: A two-compartment model of tacrolimus could best describe the data from the two populations. The final model including two covariates, population (liver transplant recipients or volunteers) and serum ALT (alanine aminotransferase) level, was verified and adequately described the pharmacokinetic characteristics of tacrolimus. The estimates of V2/F, Q/F and V3/F were 22.7 L, 76.3 L/h and 916 L, respectively. The estimated CL/F in the volunteers and liver transplant recipients was 32.8 and 18.4 L/h, respectively. Serum ALT level was inversely related to CL/F, whereas age did not influence CL/F. Thus, the elderly (>= 65 years) and adult (<65 years) groups in the liver transplant recipients showed no significant difference in the clearance of tacrolimus.

Conclusion: Compared with using the sparse data only, the integrating modeling technique combining sparse data from the patients and dense data from the healthy volunteers improved the PopPK analysis of tacrolimus.

语种英语
WOS记录号WOS:000349333700014
引用统计
被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60345
专题北京大学药学院_药剂学系
作者单位1.Gen Hosp Armed Police Forces, Beijing 100039, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China
3.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Lu, Yan-xia,Su, Qing-hong,Wu, Ke-hua,et al. A population pharmacokinetic study of tacrolimus in healthy Chinese volunteers and liver transplant patients[J]. ACTA PHARMACOLOGICA SINICA,2015,36(2):281-288.
APA Lu, Yan-xia.,Su, Qing-hong.,Wu, Ke-hua.,Ren, Yu-peng.,Li, Liang.,...&Lu, Wei.(2015).A population pharmacokinetic study of tacrolimus in healthy Chinese volunteers and liver transplant patients.ACTA PHARMACOLOGICA SINICA,36(2),281-288.
MLA Lu, Yan-xia,et al."A population pharmacokinetic study of tacrolimus in healthy Chinese volunteers and liver transplant patients".ACTA PHARMACOLOGICA SINICA 36.2(2015):281-288.
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