Comparison of the inhibitory effects of tolcapone and entacapone against human UDP-glucuronosyltransferases
文献类型：期刊论文
| 作者 | Lv, Xia1,2; Wang, Xin-Xin3; Hou, Jie4; Fang, Zhong-Ze3; Wu, Jing-Jing1,2; Cao, Yun-Feng3; Liu, Shu-Wen1; Ge, Guang-Bo1,2; Yang, Ling2,5 |
| 刊名 | TOXICOLOGY AND APPLIED PHARMACOLOGY
 |
| 出版日期 | 2016-06-15 |
| 卷号 | 301页码:42-49 |
| 关键词 | Udp-glucosyltransferases Entacapone Tolcapone Inhibitory Effects Drug-drug Interactions (Ddi) |
| ISSN号 | 0041-008X |
| DOI | 10.1016/j.taap.2016.04.009 |
| 文献子类 | Article |
| 英文摘要 | Tolcapone and entacapone are two potent catechol-O-methyltransferase (COMT) inhibitors with a similar skeleton and displaying similar pharmacological activities. However, entacapone is a very safe drug used widely in the treatment of Parkinson's disease, while tolcapone is only in limited use for Parkinson's patients and needs careful monitoring of hepatic functions due to hepatotoxicity. This study aims to investigate and compare the inhibitory effects of entacapone and tolcapone on human UDP-glucosyltransferases (UGTs), as well as to evaluate the potential risks from the view of drug-drug interactions (DDI). The results demonstrated that both tolcapone and entacapone exhibited inhibitory effects on UGT1A1, UGT1A7, UGT1A9 and UGT1A10. In contrast to entacapone, tolcapone exhibited more potent inhibitory effects on UGT1A1, UGT1A7, and UGT1A10, while their inhibitory potentials against UGT1A9 were comparable. It is noteworthy that the inhibition constants (K-i) of tolcapone and entacapone against bilirubin-O-glucuronidation in human liver microsomes (HLM) are determined as 0.68 mu M and 30.82 mu M, respectively, which means that the inhibition potency of tolcapone on UGT1A1 mediated bilirubin-O-glucuronidation in HLM is much higher than that of entacapone. Furthermore, the potential risks of tolcapone or entacapone via inhibition of human UGT1A1 were quantitatively predicted by the ratio of the areas under the plasma drug concentration-time curve (AUC). The results indicate that tolcapone may result in significant increase in AUC of bilirubin or the drugs primarily metabolized by UGT1A1, while entacapone is unlikely to cause a significant DDI through inhibition of UGT1A1. (C) 2016 Elsevier Inc All rights reserved. |
| WOS关键词 | DRUG-DRUG INTERACTIONS ; IN-VITRO ; INDUCED HYPERBILIRUBINEMIA ; BILIRUBIN GLUCURONIDATION ; CLINICAL-IMPLICATIONS ; GENETIC-POLYMORPHISM ; PARKINSONS-DISEASE ; METABOLISM ; UGT1A1 ; PHARMACOKINETICS |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000376144800005 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/170960]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 通讯作者 | Ge, Guang-Bo; Yang, Ling |
| 作者单位 | 1.Southern Med Univ, Guangdong Prov Inst Nephrol, State Key Lab Organ Failure Res, Guangzhou 510515, Guangdong, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China 3.RSKT Biopharma Inc, Dalian 116023, Peoples R China 4.Dalian Med Univ, Dalian 116044, Peoples R China 5.Jiangxi Univ Tradit Chinese Med, Nanchang 330006, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lv, Xia,Wang, Xin-Xin,Hou, Jie,et al. Comparison of the inhibitory effects of tolcapone and entacapone against human UDP-glucuronosyltransferases[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2016,301:42-49. |
| APA | Lv, Xia.,Wang, Xin-Xin.,Hou, Jie.,Fang, Zhong-Ze.,Wu, Jing-Jing.,...&Yang, Ling.(2016).Comparison of the inhibitory effects of tolcapone and entacapone against human UDP-glucuronosyltransferases.TOXICOLOGY AND APPLIED PHARMACOLOGY,301,42-49. |
| MLA | Lv, Xia,et al."Comparison of the inhibitory effects of tolcapone and entacapone against human UDP-glucuronosyltransferases".TOXICOLOGY AND APPLIED PHARMACOLOGY 301(2016):42-49. |
入库方式： OAI收割
来源：大连化学物理研究所
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