Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous DA-8159, a new erectogenic, in rats

被引:17
作者
Kim, YC
Shim, HJ
Lee, JH
Kim, SH
Kwon, JW
Kim, WB
Lee, MG
机构
[1] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea
[2] Seoul Natl Univ, Res Inst Pharmaceut Sci, Seoul 151742, South Korea
[3] Dong A Pharmaceut Co, Res Lab, Yongin, South Korea
关键词
DA-8159; DA-8164; enzyme inducers and inhibitors; CYP isozymes; pharmacokinetics; rats;
D O I
10.1002/bdd.453
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In order to find what types of hepatic microsomal cytochrome P450 (CYP) isozymes are involved in the metabolism of DA-8159 and in the formation of DA-8164 in rats, enzyme inducers, such as dexamethasone, phenobarbital, 3-methylcholanthrene and isoniazid, and enzyme inhibitors, such as troleandomycin and quinine, were pretreated in rats. After a 1 min intravenous administration of DA-8159 at a dose of 30 mg/kg to rats pretreated with dexamethasone (a main inducer of CYP3A1/2 in rats), the total areas under the plasma concentration-time curve from time zero to time infinity (AUC) values of DA-8159 (283 versus 349 mu g min/ml) and DA-8164 (98.0 versus 79.8 mu g min/ml) were significantly smaller and greater, respectively, than those in control rats. However, the AUC values of DA-8159 were not significantly different after pretreatment with phenobarbital, isoniazid and 3-methylcholanthrene (main inducers of CYP2B1/2, 2E1 and 1A1/2, respectively, in rats). In rats pretreated with troleandomycin (a main inhibitor of CYP3A1/2 in rats), the AUC values of DA-8159 (435 versus 370 mu g min/ml) and DA-8164 (34.8 versus 76.5 mu g min/ml) were significantly greater and smaller, respectively However, in rats pretreated with quinine (a main inhibitor of CYP2D1 in rats), the AUC of DA-8159 was comparable to that in control rats. The above data indicate that DA-8159 was metabolized and DA-8164 was formed mainly via CYP3A1/2 in rats. Copyright (c) 2005 John Wiley & Sons, Ltd.
引用
收藏
页码:233 / 241
页数:9
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