Mechanism of drug-drug interactions between warfarin and statins.

机译：华法林与他汀类药物之间药物相互作用的机制。

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The anticoagulant drug warfarin and the lipid lowering statin drugs are commonly co-administered to patients with cardiovascular disease. Clinically significant drug-drug interactions (DDIs) between these drugs have been recognized for many years, but the biochemical mechanisms causing these interactions have not been explained fully. Previous theories include kinetic alterations in CYP-mediated drug metabolism or disturbances of drug-protein binding to serum albumin. However, neither the enantioselective effects on warfarin metabolism nor the potential disruption of drug transporter function have been well investigated. It was the purpose of this research project to further explore the etiology of the DDIs between warfarin and several statin drugs in order to inform safer prescribing practices. An analytical method was successfully developed and validated to study the mechanism of DDIs. Role of different ADME properties was evaluated to understand the mechanism of these DDIs. The results showed that different statins show different mechanisms, CYP mediated inhibition of warfarin metabolism by statins being the major cause for these DDIs contributing to the DDIs of all the statins. PPB displacement may play a role in DDIs between warfarin and fluvastatin, but it does not play any role in DDIs involving warfarin with other statins. Tested drug transporters did not play any role in these DDIs.

机译：抗凝药物华法林和降脂他汀类药物通常共同给予患有心血管疾病的患者。这些药物之间的临床意义重大的药物-药物相互作用（DDI）已被公认多年，但是导致这些相互作用的生化机制尚未得到充分解释。先前的理论包括CYP介导的药物代谢的动力学改变或药物-蛋白与血清白蛋白结合的紊乱。但是，对华法林代谢的对映选择性作用和对药物转运蛋白功能的潜在破坏均未得到充分研究。该研究项目的目的是进一步探索华法林与几种他汀类药物之间DDIs的病因，以便为更安全的处方提供依据。成功地开发了一种分析方法，并进行了验证，以研究DDI的机理。评估了不同ADME属性的作用以了解这些DDI的机理。结果表明，不同的他汀类药物表现出不同的机制，CYP介导的他汀类药物对华法林代谢的抑制作用是这些DDI促成所有他汀类药物DDI的主要原因。 PPB置换可能在华法林与氟伐他汀之间的DDI中起作用，但在涉及华法林与其他他汀类药物的DDI中不起作用。经过测试的药物转运蛋白在这些DDI中没有任何作用。

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作者
Shaik, Abdul Naveed.;
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Massachusetts College of Pharmacy and Health Sciences.;

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授予单位 Massachusetts College of Pharmacy and Health Sciences.;
学科 Pharmaceutical sciences.;Pharmacology.
学位 Ph.D.
年度 2015
页码 233 p.
总页数 233
原文格式 PDF
正文语种 eng
中图分类生物数学方法;
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1. Direct and indirect mechanisms in warfarin drug-drug interactions: fact or fiction? [J] . Duwez M., Chanoine S., Martel B., International journal of clinical pharmacy. . 2016,第2期

机译：华法林药物相互作用中的直接和间接机制：事实还是虚构？
2. Mechanism of drug-drug interactions between warfarin and statins [J] . Shaik Abdul Naveed, Grater Richard, Lulla Mukesh, Drug Metabolism Reviews . 2016,第1a4期

机译：华法林与他汀类药物相互作用的机理
3. Mechanism of drug-drug interactions between warfarin and statins [J] . Shaik Abdul Naveed, Grater Richard, Lulla Mukesh, Drug Metabolism Reviews . 2016,第1a4期

机译：华法林和他汀类药物 - 药物相互作用的机制
4. Mining drug-drug interaction patterns from linked data: A case study for Warfarin, Clopidogrel, and Simvastatin [C] . Pathak J., Kiefer R.C., Chute C.G. IEEE International Conference on Bioinformatics and Biomedicine . 2013

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5. Prediction of drug-drug interaction between warfarin and nafcillin using PBPK modeling [D] . Harshith, Neeli. 2018

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6. Drug-drug interactions and risk of bleeding among inpatients on warfarin therapy: a prospective observational study [O] . Gebrehiwot Teklay, Nuredin Shiferaw, Befikadu Legesse, 2014

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7. Identifying drug-drug interactions by data mining a pilot study of warfarin-associated drug interactions:a pilot study of warfarin-associated drug interactions [O] . Hansen, Peter Wæde, Clemmensen, Line, Sehested, Thomas S. G., 2016

机译：通过数据挖掘确定药物 - 药物相互作用华沙林相关药物相互作用的初步研究：华法林相关药物相互作用的初步研究

Mechanism of drug-drug interactions between warfarin and statins.

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