The Influence of Age and Sex on the Clearance of Cytochrome P450 3A Substrates
作者:
Monette M Cotreau,
Lisa L von Moltke,
David J Greenblatt,
期刊:
Clinical Pharmacokinetics
(ADIS Available online 2005)
卷期:
Volume 44,
issue 1
页码: 33-60
ISSN:0312-5963
年代: 2005
出版商: ADIS
关键词: Elderly;Cytochrome P450 inhibitors, pharmacokinetics;Sex hormones
数据来源: ADIS
摘要:
Cytochrome P450s (CYPs) are an important family of enzymes in the metabolism of many therapeutic agents and endogenous metabolic reactions. The CYP3A subfamily is especially prominent in these metabolic activities. This review article focuses on how the factors of age and sex may influence thein vivoactivity of human CYP3A. The functional activity of CYP3A varies based on issues such as interaction with one or more substrates and between individuals and/or localisation. For CYP3A substrates, intrinsic clearance is the component of total clearance that is contributed by the enzymes. Depending on the route of administration and the contribution of hepatic blood flow to overall clearance, sensitivities to changes in CYP3A activities may differ. Additionally, age may influence the hepatic blood flow and, in turn, affect CYP3A activity. A review of the literature regarding age influences on the clearance of CYP3A substrates does suggest that age can affect the clearance of certain CYP3A substrates.CYP3A is responsible for a large number of endogenous metabolic reactions involving steroid hormones, and enzyme activity has been reported to be induced and/or inhibited in the presence of some sex steroids. Based on published studies for most CYP3A substrates, sex does not appear to influence clearance; however, with certain substrates significant sex-related differences are found. In such cases, women primarily have higher clearance than men.
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