当前位置： SCI文献检索 > EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY期刊下所有文献 > Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil.

Pregnancy and use of oral contraceptives reduces the biotransformation of proguanil to cycloguanil.

Abstract：

OBJECTIVE:To determine the effects of late pregnancy and also oestrogen supplementation on the CYP2C19-mediated biotransformation of proguanil (PG) to its active antifol triazine metabolite cycloguanil (CG). METHODS:Case control study conducted on the NW border of Thailand; a single dose of PG (4 mg/kg) was administered to Karen women in late pregnancy and a single blood and urine sample taken 6 h later. Women were studied in late pregnancy (>36 weeks) and restudied 2 months after delivery. A separate cohort of Karen women newly attending a birth-control clinic were studied before and 3 weeks into their first course of oral contraceptives (OCP: levonorgestrel 0.15 mg and ethinyloestradiol 0.03 mg). Forty-five pregnant women and forty-two healthy OCP users were studied. RESULTS:The results were similar in both groups; pregnancy and OCP use were both associated with reduced formation of cycloguanil (CG). Impaired PG biotransformation was seen in women with the "extensive metaboliser" phenotype (urine PG/CG ratio <10). CG levels, adjusted for dose, were a median (range) 73% (-59 to 420%) higher following the pregnancy than during the pregnancy in women characterised as extensive metabolisers ( P<0.001). CG levels in women characterised as extensive metabolisers were 34% (-54 to 323%) higher before than while taking the OCP ( P<0.01). CONCLUSION:Late pregnancy and OCP use impair biotransformation of the active antimalarial metabolite CG from the parent PG. This may be mediated by oestrogen inhibition of CYP2C19 activity. The dose of PG should be increased by 50% in these groups.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

McGready R,Stepniewska K,Seaton E,Cho T,Cho D,Ginsberg A,Edstein MD,Ashley E,Looareesuwan S,White NJ,Nosten F

doi

10.1007/s00228-003-0651-x

subject

Has Abstract

pub_date

2003-10-01 00:00:00

pages

553-7

issue

7

eissn

0031-6970

issn

1432-1041

journal_volume

59

pub_type

临床试验,杂志文章

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