Pharmacokinetics and metabolism of jatrorrhizine, a gastric prokinetic drug candidate
文献类型：期刊论文
| 作者 | Shi, Rong3; Zhou, Hui3; Ma, Bingliang3; Ma, Yueming3; Wu, Dazheng4; Wang, Xinhong1; Luo, Hongfeng5 ; Cheng, Nengneng2
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| 刊名 | BIOPHARMACEUTICS & DRUG DISPOSITION
 |
| 出版日期 | 2012-04 |
| 卷号 | 33期号:3页码:135-145 |
| 关键词 | jatrorrhizine pharmacokinetics metabolism kinetics CYPs UGTs rats RLMs |
| ISSN号 | 0142-2782 |
| DOI | 10.1002/bdd.1779 |
| 文献子类 | Article |
| 英文摘要 | Jatrorrhizine, a protoberberine alkaloid derived from Coptis chinensis, is currently under investigation as a natural gastric prokinetic drug candidate. In vitro and in vivo studies were conducted to characterize its pharmacokinetics and metabolism. After intravenous administration, the plasma concentration kinetics and major metabolites in rats were investigated. The metabolic kinetics, key cytochrome P450 enzymes and UDP-glucuronosyltransferase isoforms (UGTs) of jatrorrhizine were studied in rat liver microsomes (RLMs). After intravenous administration, plasma jatrorrhizine concentrations showed a biphasic decline, dose-independent clearance and half-life of terminal elimination phase, and a relatively large distribution volume. The metabolic pathway for the conversion of jatrorrhizine was important for its elimination. In addition, the demethylated and glucuronidated products were found to be the major metabolites in rats. The enzyme kinetics for both demethylation and glucuronidation were fitted to the hyperbolic Michaelis-Menten equation in RLMs. CYP3A1/2 and CYP2D2 were mainly responsible for demethylation, and UGT 1A1 and 1A3 were responsible for glucuronidation in RLMs. The metabolic properties of jatrorrhizine suggest multiple metabolic pathways. These results will contribute to promote further research and development of jatrorrhizine. Copyright (c) 2012 John Wiley & Sons, Ltd. |
| WOS关键词 | RAT-LIVER-MICROSOMES ; HUMAN UDP-GLUCURONOSYLTRANSFERASES ; CYTOCHROME-P450 INHIBITORS ; IN-VITRO ; MASS-SPECTROMETRY ; GLUCURONIDATION ; IDENTIFICATION ; BIOTRANSFORMATION ; SELECTIVITY ; BERBERINE |
| 资助项目 | Shanghai Institutions of Higher Education[00000000] ; National Natural Science foundation of China[30873231] ; Shanghai Science and Technology Committee[07DZ19718] ; Shanghai University of Traditional Chinese Medicine[00000000] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000302354300002 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278132]  |
| 专题 | 天然药物化学研究室 |
| 通讯作者 | Ma, Yueming |
| 作者单位 | 1.Shanghai Univ Tradit Chinese Med, Dept Chem, Shanghai 201203, Peoples R China; 2.Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China 3.Shanghai Univ Tradit Chinese Med, Pharmacokinet Lab, Shanghai 201203, Peoples R China; 4.Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Med, Shanghai 201203, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Shi, Rong,Zhou, Hui,Ma, Bingliang,et al. Pharmacokinetics and metabolism of jatrorrhizine, a gastric prokinetic drug candidate[J]. BIOPHARMACEUTICS & DRUG DISPOSITION,2012,33(3):135-145. |
| APA | Shi, Rong.,Zhou, Hui.,Ma, Bingliang.,Ma, Yueming.,Wu, Dazheng.,...&Cheng, Nengneng.(2012).Pharmacokinetics and metabolism of jatrorrhizine, a gastric prokinetic drug candidate.BIOPHARMACEUTICS & DRUG DISPOSITION,33(3),135-145. |
| MLA | Shi, Rong,et al."Pharmacokinetics and metabolism of jatrorrhizine, a gastric prokinetic drug candidate".BIOPHARMACEUTICS & DRUG DISPOSITION 33.3(2012):135-145. |
入库方式： OAI收割
来源：上海药物研究所
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