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学科主题: 临床医学
题名:
Association of CYP3A4*18B polymorphisms with the pharmacokinetics of cyclosporine in healthy subjects
作者: Hu, Y.-F.; Tu, J.-H.; Tan, Z.-R.; Liu, Z.-Q.; Zhou, G.; He, J.; Wang, D.; Zhou, H.-H.
关键词: CYP3A4 ; polymorphisms ; cyclosporine ; pharmacokinetics
刊名: XENOBIOTICA
发表日期: 2007-03-01
DOI: 10.1080/00498250601149206
卷: 37, 期:3, 页:315-327
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy ; Toxicology
研究领域[WOS]: Pharmacology & Pharmacy ; Toxicology
关键词[WOS]: HUMAN-LIVER ; CYP3A4 ; IDENTIFICATION ; CHINESE ; CYTOCHROME-P-450 ; METABOLISM ; REJECTION ; CYP2C19 ; PHARMACOGENOMICS ; INHIBITORS
英文摘要:

The aim of this study is to evaluate the association of the CYP3A4(*) 18B genotype with the cyclosporine metabolism in healthy subjects. We employed PCR RFLP assays for analysis of the CYP3A4(*)18B genotype. Each of 26 subjects, comprising 12 CYP3A4(*)1/(*)l, 12 CYP3A4(*)1/(*)18B and 2 CYP3A4(*)18B/(*)18B, was given a single oral dose of cyclosporine (4mgkg(-1)). The plasma concentrations of cyclosporine were measured for up to 24h post dose by high-performance liquid chromatography-electrospray mass spectrometry. We found that the mean C-max (95% confidence intervals) of cyclosporine were 2237 (2905, 1859) ((*)1/(*)1), 2247 (2916, 1869) ((*)1/(*)18B), and 905 (1192,506) ngml(-1) ((*)18B/(*1)8B)(p=0.037) and the mean AUCO-4were 5026 (6181, 4372) ((*)1/(*)1), 4434 (5481, 3841) ((*)1/(*)18B) and 2561 (3155, 1736) ng ml-1 h ((*)18B/(*)18B)(p=0.02l). The CL in the (*)18B/(*)18B group was significantly higher than in the (*)1/(*)1 group. However, T-maz exhibited no difference among the three genotypes. (*)18B/(*)18B group showed 50% reduction in concentration at 2h post dose compared with (*)1/(*)18B (p=0.062) or (*)1/(*)1 (p=0.047), but no statistical significance was detected between *1/(*)1 and *1/*18B groups (p > 0.05). The data suggest that the CYP3A4(*)18B genotype affects cyclosporine pharmacokinetics probably resulting from a higher enzymatic activity of this mutation in healthy subjects.

语种: 英语
WOS记录号: WOS:000245984500007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56128
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: 1.Cent S Univ, Inst Clin Pharmacol, Pharmacogenet Res Inst, Changsha 410078, Hunan, Peoples R China
2.Peking Univ, Hosp 3, Beijing 100871, Peoples R China

Recommended Citation:
Hu, Y.-F.,Tu, J.-H.,Tan, Z.-R.,et al. Association of CYP3A4*18B polymorphisms with the pharmacokinetics of cyclosporine in healthy subjects[J]. XENOBIOTICA,2007,37(3):315-327.
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