Role of rat liver cytochrome P450 3A and 2D in metabolism of imrecoxib
文献类型：期刊论文
| 作者 | Xu HY1; Xie ZY1; Zhang P1; Sun J1; Chu FM1; Guo ZR1; Zhong DF1 |
| 刊名 | ACTA PHARMACOLOGICA SINICA
 |
| 出版日期 | 2006 |
| 卷号 | 27期号:3页码:372-380 |
| 关键词 | NONSTEROIDAL ANTIINFLAMMATORY DRUGS COX-2 INHIBITORS IN-VITRO MICROSOMES CYCLOOXYGENASE-2 OSTEOARTHRITIS ISOENZYMES NSAIDS VIVO imrecoxib cytochrome P450 metabolism liver microsomes |
| ISSN号 | 1671-4083 |
| 其他题名 | Role of rat liver cytochrome P450 3A and 2D in metabolism of imrecoxib |
| 英文摘要 | Aim: To investigate the in vitro metabolism of imrecoxib in rat liver microsomes and to identify the cytochrome P450 (CYP) forms involved in its metabolism. Methods: Liver microsomes of Wistar rats were prepared using an ultracentrifuge. The in vitro metabolism of imrecoxib was studied by incubation with rat liver microsomes. To characterize the CYP forms involved in the 4'-methyl hydroxylation of imrecoxib, the effects of typical CYP inducers (such as dexamethasone, isoniazid and beta-naphthoflavone) and of CYP inhibitors (such as ketoconazole, quinine, alpha-naphthoflavone, methylpyrazole, and cimetidine) on the formation rate of 4'-hydroxymethyl imrecoxib were investigated. Results: Imrecoxib was metabolized to 3 metabolites by rat liver microsomes: 4'-hydroxymethyl imrecoxib (M4), 4'-hydroxymethyl-5-hydoxyl imrecoxib (M3), and 4'-hydroxymethyl-5-car-bonyl imrecoxib (M5). Over the imrecoxib concentration range studied (5-600 mu mol/L), the rate of 4'-methyl hydroxylation conformed to monophasic Michaelis-Menten kinetics. Dexamethasone significantly induced the formation of M4. Ketoconazole markedly lowered the metabolic rate of imrecoxib in a concentration-dependent manner. Moreover, a significant inhibitory effect of quinine on the formation of M4 was observed in microsomes obtained from control rats, isoniazid-induced rats, and beta-naphthoflavone-induced rats. In contrast, alpha-naphthoflavone, cimetidine, and methylpyrazole had no inhibitory effects on this metabolic pathway. Conclusion: Imrecoxib is metabolized via 4'-methyl hydroxylation in rat liver microsomes. The reaction is mainly catalyzed by CYP 3 A. CYP 2D also played a role in control rats, in isoniazid-induced rats and in beta-naphthoflavone-induced rats. |
| 语种 | 英语 |
| CSCD记录号 | CSCD:2621336 |
| 源URL | [http://ir.imr.ac.cn/handle/321006/143850]  |
| 专题 | 金属研究所_中国科学院金属研究所 |
| 作者单位 | 1.中国科学院金属研究所 2.Peking Union Med Coll 3.中国科学院 |
| 推荐引用方式 GB/T 7714 | Xu HY,Xie ZY,Zhang P,et al. Role of rat liver cytochrome P450 3A and 2D in metabolism of imrecoxib[J]. ACTA PHARMACOLOGICA SINICA,2006,27(3):372-380. |
| APA | Xu HY.,Xie ZY.,Zhang P.,Sun J.,Chu FM.,...&Zhong DF.(2006).Role of rat liver cytochrome P450 3A and 2D in metabolism of imrecoxib.ACTA PHARMACOLOGICA SINICA,27(3),372-380. |
| MLA | Xu HY,et al."Role of rat liver cytochrome P450 3A and 2D in metabolism of imrecoxib".ACTA PHARMACOLOGICA SINICA 27.3(2006):372-380. |
入库方式： OAI收割
来源：金属研究所
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