当前位置： SCI文献检索 > EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > Variability of coumarin 7- and 3-hydroxylation in a Jordanian population is suggestive of a functional polymorphism in cytochrome P450 CYP2A6.

Variability of coumarin 7- and 3-hydroxylation in a Jordanian population is suggestive of a functional polymorphism in cytochrome P450 CYP2A6.

Abstract：

OBJECTIVE:To determine the variability of coumarin 7- and 3-hydroxylation in a human population and to evaluate the evidence for the existence of genetic polymorphism in these pathways. 7-Hydroxylation of coumarin is considered to be a detoxication pathway, whilst 3-hydroxylation, which predominates in rats, leads to hepatotoxicity in the rat. Coumarin metabolic phenotypes could aid in refining the risk evaluation for humans of dietary and environmental exposure to coumarin and for the chronic use of coumarin in high doses as a drug to treat lymphoedema and certain cancers. METHODS:Healthy male and female Jordanian volunteers (n = 103) were administered 2 mg coumarin by mouth and collected their 0-8-h urines. These, together with pre-dose blank urines, were analysed by selected-ion monitoring gas chromatography mass spectrometry for their content of the coumarin metabolites 7-hydroxycoumarin (70HC) and 2-hydroxyphenylacetic acid (2OHPAA), the latter arising from the 3-hydroxylation pathway. RESULTS:After coumarin administration, excretion of both 70HC and 2OHPAA was highly variable. A coumarin metabolic ratio (2OHPAA/7OHC) was suggestive of polymorphism. At least one subject had a metabolic response similar to an individual known to be both phenotypically and genotypically (CYP2A6 gene) 7-hydroxylation-deficient. CONCLUSION:In the light of the finding of high variability and possible polymorphism in both the 7- and 3-hydroxylation of coumarin in a human population. we recommend a reappraisal of the risk evaluation of human exposure to coumarin, particularly in pharmaceutical doses.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Hadidi H,Irshaid Y,Vågbø CB,Brunsvik A,Cholerton S,Zahlsen K,Idle JR

doi

10.1007/s002280050489

subject

Has Abstract

pub_date

1998-07-01 00:00:00

pages

437-41

issue

5

eissn

0031-6970

issn

1432-1041

journal_volume

54

pub_type

杂志文章

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