Schematic illustration of the interaction between CYP2C8 and its glucuronide substrates. Schematic illustration of the interaction between CYP2C8 and its.

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CYP2C8 and Drug Interactions

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Schematic illustration of the interaction between CYP2C8 and its glucuronide substrates. Schematic illustration of the interaction between CYP2C8 and its glucuronide substrates. CYP2C8 and the UGT are localized on opposite sites of the endoplasmic membrane (A). The drug is glucuronidated by the UGT (B). Hereafter, the glucuronide crosses the endoplasmic membrane and binds into CYP2C8 (C). Then, the glucuronide is either metabolized by CYP2C8 and released as a metabolite (D, left), e.g., desloratadine glucuronide, and diclofenac acyl glucuronide, or it is metabolized to a reactive agent that inactivates CYP2C8 (D, right), as for clopidogrel acyl 1-β-d-glucuronide and gemfibrozil 1-O-β glucuronide. CYP2C8 has been suggested to exist as a dimer (Hu et al., (2010), Schoch et al., (2004)). ER, endoplasmic reticulum. Janne T. Backman et al. Pharmacol Rev 2016;68:168-241 Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics