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学科主题: 临床医学
题名:
Population pharmacokinetic study of methotrexate in children with acute lymphoblastic leukemia
作者: Zhang, C.1,2; Zhai, S.1,2; Yang, L.3; Wu, H.3; Zhang, J.3; Ke, X.4
关键词: population pharmacokinetic ; methotrexate ; NONMEM ; acute lymphoblastic leukemia
刊名: INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS
发表日期: 2010
卷: 48, 期:1, 页:11-21
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: HIGH-DOSE METHOTREXATE ; ACUTE LYMPHOCYTIC-LEUKEMIA ; BAYESIAN-ESTIMATION ; YOUNG-ADULTS ; PHARMACODYNAMICS ; OSTEOSARCOMA ; ELIMINATION ; VARIABILITY ; PARAMETERS ; CHILDHOOD
英文摘要:

A Population pharmacokinetic model was developed to describe the factors that may affect die pharmacokinetics of methotrexate (MTX) in Chinese child patients with acute lymphoid leukemia (ALL) and to predict the individual pharmacokinetic parameters in these patients. One hundred and eighteen children with ALL who received MTX at the dose of 2-3.5 g/m(2) were enrolled ill this Study. 96 children were enrolled in the index group and 22 children in the validation group. The data were analyzed using nonlinear mixed effect model (NONMEM) software. A linear two-compartment model with linear elimination best described the data. The forward inclusion-backward elimination method was used to Investigate the different covariates, including age, body weight, gender, etc. The Bayesian method was used to predict the individual pharmacokinetic parameters. Validation was applied using ail internal and external approach. The population pharmacokinetic parameters and 95% confidence interval (CI) were obtained as follows: The clearance of central compartment (CL I), apparent volume of distribution of central compartment (V 1), the clearance between central and peripheral compartment (CL2), and apparent volume of distribution of peripheral compartment (V2) were 5.04 (3.93 - 6.15) l/min, 16.1 (12.5 - 19.7)1,0.203 (0.102 - 0.304) l/min and 7.05 (3.86 - 10.20) 1, respectively. The inter-individual variability of CL1, VI, CL2, and V2 were 49.60%, 29.36%, 137.64%, and 107.70%, respectively. Gender, body surface area and the amount of alkalinization agent during 24 hours before MTX administration had significant effects oil CL1. A strong relationship was found ill this Study between CL2 and age, as well as between V2 and age. A good correlation was further proved through the validation model. Moreover, some secondary pharmacokinetic parameters were estimated: the elimination half-life t(1/2) was 2.34 11 (CV = 36.7%), elimination constant k(e) was 0.33 h(-1) (CV = 33.2%), and the area under plasma concentration versus time curve AUC was 582.92 mg.h.l(-1) (CV = 55.9%). Our model combine Bayesian approach enabled a satisfactory estimation of MTX concentration in individual patients. The results Of this study allowed clinicians to assess the MTX pharmacokinetic parameters based oil the specific demographic characteristics of patients.

语种: 英语
WOS记录号: WOS:000275346300002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65717
Appears in Collections:北京大学第三临床医学院_药剂科_期刊论文

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作者单位: 1.Peking Univ, Hosp 3, Dept Pharm, Beijing 100191, Peoples R China
2.Peking Univ, Therapeut Drug Monitoring & Clin Toxicol Ctr, Beijing 100191, Peoples R China
3.Affiliated Hosp 1, Kunming Med Sch, Dept Pharm, Kunming, Peoples R China
4.Peking Univ, Hosp 3, Dept Hematol, Beijing 100191, Peoples R China

Recommended Citation:
Zhang, C.,Zhai, S.,Yang, L.,et al. Population pharmacokinetic study of methotrexate in children with acute lymphoblastic leukemia[J]. INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS,2010,48(1):11-21.
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