KINETIC AND INHIBITOR STUDIES OF ACETAMINOPHEN AND ZIDOVUDINE GLUCURONIDATION IN RAT-LIVER MICROSOMES

被引：10

作者：

AMEER, B ^{[1
]}

JAMES, MO ^{[1
]}

SALEH, J ^{[1
]}

机构：

[1] UNIV FLORIDA,COLL PHARM,GAINESVILLE,FL 32610

来源：

DRUG AND CHEMICAL TOXICOLOGY | 1992年 / 15卷 / 02期

关键词：

D O I：

10.3109/01480549209032297

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The antiviral drug zidovudine (ZDV) and the analgesic and antipyretic agent acetaminophen (AP) are both biotransformed in the liver of humans to ether glucuronides. A previous clinical trial of ZDV suggested the potential for a clinically significant interaction between AP and ZDV, probably based upon competing hepatic metabolism. To study the mechanism of this potential competition between AP and ZDV as substrates for uridine diphosphoglucuronyltransferase (UDPGT), enzyme kinetic studies were performed using rat liver microsome preparations. Cross inhibition studies demonstrated that AP glucuronidation was competitively inhibited by ZDV, while ZDV glucuronidation was slightly inhibited by AP in a noncompetitive interaction.

引用

页码：161 / 175

页数：15

共 18 条

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