Role of CYP3A in Isoniazid Metabolism In Vivo
文献类型：期刊论文
| 作者 | Liu, Ke1; Li, Feng2; Lu, Jie1; Gao, Zhiwei3 ; Klaassen, Curtis D.2; Ma, Xiaochao1
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| 刊名 | DRUG METABOLISM AND PHARMACOKINETICS
 |
| 出版日期 | 2014-04-25 |
| 卷号 | 29期号:2页码:219-222 |
| 关键词 | isoniazid metabolism cytochrome P450 3A hepatotoxicity mice |
| ISSN号 | 1347-4367 |
| DOI | 10.2133/dmpk.DMPK-13-NT-089 |
| 文献子类 | Article |
| 英文摘要 | Isoniazid (INH), a first-line drug for tuberculosis control, frequently causes liver injury. Multiple previous reports suggest that CYP3A is involved in INH metabolism, bioactivation and hepatotoxicity, although direct evidence is unavailable. In the current study, wild-type and Cyp3a-null mice were used to determine the potential role of Cyp3a in INH metabolism in vivo. Compared to wild-type mice, there were no significant differences in the pharmacokinetic profiles of INH or acetyl-isoniazid in Cyp3a-null mice after an oral administration of 50mg/kg INH. With the same treatment, distribution of INH and its major metabolites was similar in the liver of wild-type and Cyp3a-null mice. A reactive metabolite of INH was trapped by N-alpha-acetyl-L-lysine in mouse liver microsomes, but Cyp3a does not contribute to this bioactivation pathway. In addition, no liver injury was observed in wild-type or Cyp3a-null mice treated with 60 or 120mg/kg INH. In summary, Cyp3a has no effect on systemic pharmacokinetics of INH in mice. Further studies are needed to determine whether and how exactly CYP3A is involved in INH bioactivation and hepatotoxicity. |
| WOS关键词 | DRUG-INDUCED HEPATOTOXICITY ; N-ACETYLTRANSFERASE 2 ; GENETIC POLYMORPHISMS ; INDUCED HEPATITIS ; COVALENT BINDING ; LIVER-INJURY ; SUSCEPTIBILITY ; BIOACTIVATION ; ASSOCIATION ; GENOTYPE |
| 资助项目 | National Institute of Diabetes and Digestive and Kidney Diseases[DK090305] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000334596600018 |
| 出版者 | JAPANESE SOC STUDY XENOBIOTICS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277109]  |
| 专题 | 上海药物代谢研究中心 |
| 通讯作者 | Ma, Xiaochao |
| 作者单位 | 1.Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Ctr Pharmacogenet, Pittsburgh, PA 15261 USA; 2.Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Ke,Li, Feng,Lu, Jie,et al. Role of CYP3A in Isoniazid Metabolism In Vivo[J]. DRUG METABOLISM AND PHARMACOKINETICS,2014,29(2):219-222. |
| APA | Liu, Ke,Li, Feng,Lu, Jie,Gao, Zhiwei,Klaassen, Curtis D.,&Ma, Xiaochao.(2014).Role of CYP3A in Isoniazid Metabolism In Vivo.DRUG METABOLISM AND PHARMACOKINETICS,29(2),219-222. |
| MLA | Liu, Ke,et al."Role of CYP3A in Isoniazid Metabolism In Vivo".DRUG METABOLISM AND PHARMACOKINETICS 29.2(2014):219-222. |
入库方式： OAI收割
来源：上海药物研究所
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