TY - JOUR T1 - Development of an Ecofriendly Anticoagulant Rodenticide Based on the Stereochemistry of Difenacoum JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1872 LP - 1880 DO - 10.1124/dmd.116.071688 VL - 44 IS - 12 AU - Marlène Damin-Pernik AU - Bernadette Espana AU - Stéphane Besse AU - Isabelle Fourel AU - Hervé Caruel AU - Florence Popowycz AU - Etienne Benoit AU - Virginie Lattard Y1 - 2016/12/01 UR - http://dmd.aspetjournals.org/content/44/12/1872.abstract N2 - Difenacoum, an antivitamin K anticoagulant, has been widely used as rodenticide to manage populations of rodents. Difenacoum belongs to the second generation of anticoagulant, and, as all the molecules belonging to the second generation of anticoagulant, difenacoum is often involved in primary poisonings of domestic animals and secondary poisonings of wildlife by feeding contaminated rodents. To develop a new and ecofriendly difenacoum, we explored in this study the differences in properties between diastereomers of difenacoum. Indeed, the currently commercial difenacoum is a mixture of 57% of cis-isomers and 43% of trans-isomers. Cis- and trans-isomers were thus purified on a C18 column, and their respective pharmacokinetic properties and their efficiency to inhibit the coagulation of rodents were explored. Tissue persistence of trans-isomers was shown to be shorter than that of cis-isomers with a half-life fivefold shorter. Efficiency to inhibit the vitamin K epoxide reductase activity involved in the coagulation process was shown to be similar between cis- and trans-isomers. The use of trans-isomers of difenacoum allowed to drastically reduce difenacoum residues in liver and other tissues of rodents when the rodent is moribund. Therefore, secondary poisonings of wildlife should be decreased by the use of difenacoum largely enriched in trans-isomers. ER -