Endogenous cortisol 6 beta-hydroxylation clearance is not an accurate probe for overall cytochrome P450 3A phenotyping in humans

doi:10.1016/j.cca.2009.07.017

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	Endogenous cortisol 6 beta-hydroxylation clearance is not an accurate probe for overall cytochrome P450 3A phenotyping in humans
	Hu, Zhe-Yi 3,4; Zhao, Yuan-Sheng 3,4; Wu, Di 1; Cheng, Ze-Neng 2
刊名	CLINICA CHIMICA ACTA
	2009-10-01
卷号	408 期号:1-2 页码:92-97
关键词	CYP3A Cortisol 6 beta-hydroxycortisol Midazolam
ISSN号	0009-8981
DOI	10.1016/j.cca.2009.07.017
文献子类	Article
英文摘要	Background: We determined if endogenous cortisol 6 beta-hydroxylation clearance [CL(m(6 beta))] could be used as a reliable index for in vivo CYP3A phenotyping (including both hepatic and intestinal CYP3A activities). Methods: In this study, 16 healthy volunteers received a single 7.5 mg oral dose of midazolam (MDZ). Blood samples were drawn up to 24 h after dosing. Urine samples were collected at various time periods after dosing. MDZ, 1-hydroxymidazolam (1-OHMDZ), cortisol (F) and 6 beta-hydroxycortisol (6 beta-OHF) in plasma or urine were determined by high-performance liquid chromatography with ultraviolet absorbance detection (HPLC-UV). Results: CL(m(6 beta)) was poorly correlated (P>0.2) with MDZ oral clearance [CL(oral(MDZ))] and the ratio of AUC(0 ->infinity(1 -> OHMDZ)) versus AUC(0 ->infinity(MDZ)) [MR((AUC))]. However, when examining the data obtained from male volunteers exclusively, strong correlations were observed between CL(m(6 beta)) and CL(oral(MDZ)). Larger interindividual and intraindividual variabilities were observed in urinary ratio of 6 beta-OHF/F compared with CL(m(6 beta)). Conclusion: CL(m(6 beta)) cannot reflect the overall CYP3A activity accurately and quantitatively in the population. (C) 2009 Elsevier B.V. All rights reserved.
资助项目	Department of Health[00000000] ; Department of Science and Technology of Hunan Province, P.R. China[00000000]
WOS关键词	ULTRAVIOLET ABSORBENCY DETECTION ; ERYTHROMYCIN BREATH TEST ; CYP3A ACTIVITY ; P-GLYCOPROTEIN ; HEPATIC CYP3A ; LIQUID-CHROMATOGRAPHY ; MIDAZOLAM CLEARANCE ; PLASMA ; LIVER ; 1-HYDROXYMIDAZOLAM
WOS研究方向	Medical Laboratory Technology
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000270486400019
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279112]
专题	上海药物代谢研究中心
通讯作者	Hu, Zhe-Yi
作者单位	1.Childrens Hosp Philadelphia, Abramson Res Ctr, Philadelphia, PA 19104 USA; 2.Cent S Univ, Res Inst Drug Metab & Pharmacokinet, Sch Pharmaceut Sci, Changsha 410013, Hunan, Peoples R China 3.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Hu, Zhe-Yi,Zhao, Yuan-Sheng,Wu, Di,et al. Endogenous cortisol 6 beta-hydroxylation clearance is not an accurate probe for overall cytochrome P450 3A phenotyping in humans[J]. CLINICA CHIMICA ACTA,2009,408(1-2):92-97.
APA	Hu, Zhe-Yi,Zhao, Yuan-Sheng,Wu, Di,&Cheng, Ze-Neng.(2009).Endogenous cortisol 6 beta-hydroxylation clearance is not an accurate probe for overall cytochrome P450 3A phenotyping in humans.CLINICA CHIMICA ACTA,408(1-2),92-97.
MLA	Hu, Zhe-Yi,et al."Endogenous cortisol 6 beta-hydroxylation clearance is not an accurate probe for overall cytochrome P450 3A phenotyping in humans".CLINICA CHIMICA ACTA 408.1-2(2009):92-97.