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CYP2D6 is the Major Metabolizing Enzyme of Metoclopramide
Author(s) -
Briggs Errran D.,
Bolles Amanda K.,
Livezey Mara R.,
Furge Laura Lowe
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1007.2
Subject(s) - metoclopramide , cyp2d6 , pharmacology , drug , metabolite , mechanism (biology) , antiemetic , drug interaction , nausea , pharmacogenomics , adverse effect , active metabolite , drug metabolism , medicine , chemistry , pharmacokinetics , metabolism , vomiting , cytochrome p450 , philosophy , epistemology
CYP2D6 metabolizes approximately 20% of pharmaceutical drugs. The important role that CYP2D6 plays in drug metabolism makes inactivation events clinically relevant. Thus, understanding the inactivation of CYP2D6 may prevent adverse drug‐drug interactions. Metoclopramide, a drug commonly prescribed to counteract nausea in chemotherapy patients, has previously been reported in the literature to be a mechanism‐based inhibitor of CYP2D6. We sought to expand this initial finding by constructing a metabolite profile and employing molecular modeling programs in an attempt to better understand the interactions between metoclopramide and CYP2D6. While we did not observe mechanism‐based inhibition with metoclopramide, we did observe predicted and new metabolites of metoclopramide. Furthermore, we were able to establish the relative contribution of specific P450 enzymes to the metabolic profile of metoclopramide and the role of CYP2D6 as the major metabolizer of metoclopramide. (Support: NIH 1R15‐GM086767–01 & ‐01S1).