title: Does CYP2C19 inhibition lead to clopidogrel thrombogenicity?
abstract: There exits an ongoing debate regarding potential hazards associated with concomitant use of clopidogrel and proton-pump inhibitors. In this manuscript, a meta-analysis of mortality data demonstrates that the mortality prevented by clopidogrel is significantly lower than the mortality caused by clopidogrel and proton-pump inhibitor combination. Given the hazards associated with the combination, abating the positive effect of clopidogrel is not a satisfactory explanation. Thus a hypothesis is proposed, that the combination of proton-pump inhibitors and clopidogrel increases mortality as results of thrombogenic metabolites of clopidogrel, due to inhibition of CYP2C19 by proton-pump inhibitors.
authors: Division of Internal Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. matan123@hadassah.org.il
authors: M J
authors: MJ
authors: Cohen
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004338:Drug Combinations; D004347:Drug Interactions; D006801:Humans; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D013927:Thrombosis / Q000209:etiology* / Q000401:mortality; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D004338:Drug Combinations; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine