Research Paper on Acyl Glucuronides of Gemfibrozil and Clopidogrel Inhibition of CYP2C8: Pharmacological Significance, Progress, and Challenges

Description

Title: Acyl Glucuronides of Gemfibrozil and Clopidogrel Inhibition of CYP2C8: Pharmacological Significance, Progress, and Challenges

Abstract: Gemfibrozil, a lipid-regulating drug, is an effective treatment for lowering blood triglycerides and high cholesterol. It also goes through extensive glucuronidation in addition to oxidation to create the cytochrome P450 (CYP) 2C8 known mechanism-based inactivator gemfibrozil acyl glucuronide. With the drugs metabolized by CYP2C8, such time-dependent and selective inhibition causes clinically significant drug-drug interactions (DDI). Similar to that, the acyl glucuronide of the widely used antiplatelet drug clopidogrel is a strong time-dependent CYP2C8 inhibitor that exhibits significant DDI with CYP2C8 substrates. Research on how various drugs bind to and oxidize in the CYPs active site makes up the majority of current advancements in atomic-level understanding. It is unclear how a drug’s acyl glucuronide metabolite, such as that of gemfibrozil or clopidogrel, interacts with the enzyme’s active site to inhibit it specifically. The current understanding of some significant clinical DDI brought on by gemfibrozil and clopidogrel due to the inhibition of CYP2C8 by their acyl glucuronide metabolites is summarized in this mini-review. It is significant in that it looks at current research and potential applications of structural biology tools to clarify the binding and orientation of gemfibrozil acyl glucuronide and clopidogrel acyl glucuronide in the active site close to heme that contributes to the inhibition and inactivation of CYP2C8.

Keywords: drug–drug interactions; Cytochrome P450 2C8; Gemfibrozil; Clopidogrel; Acyl Glucuronides

Paper Quality: SCOPUS / Web of Science Level Research Paper

Subject: Biomolecules

Writer Experience: 20+ Years

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