Human CYP2C19 Substrate and Inhibitor Characterization of Organophosphate Pesticides.

CYP2C19 is an important enzyme for organophosphate pesticide (OPP) metabolism. Because the OPPs can be both substrates and inhibitors of CYP2C19, we screened 45 OPPs for their ability to inhibit the activity of this enzyme and investigated the role of CYP2C19 in the metabolism of 22 of these molecules. We identified several nanomolar inhibitors of CYP2C19 as well as determined that thions, in general, are more potent inhibitors than oxons. We also determined that thions are readily metabolized by CYP2C19, although we saw no relationship between IC 50 values and intrinsic clearance rates. This study may have implications for mitigating the risk of OPP poisoning.