In vitro diazepam metabolism in horses

There is little information about drug metabolism and pharmacokinetics in horses. Therefore, it is necessary to characterize the profiles of drug metabolites for the safe use of drugs. In this study, we focused on cytochrome P450 enzymes (CYPs), which represent an important enzyme group to determine pharmacological effects of drugs. We chose diazepam as the drug of choice for this study. The aim of this study was to elucidate the metabolic pathway of diazepam in horses in comparison with rats, and to clarify CYP subfamilies responsible for diazepam metabolism in horses. Our results showed temazepam was the major diazepam metabolite produced from microsomal reactions in horse liver, but horses produced drastically less p-hydroxydiazepam as compared with rats. Furthermore, CYP3A was a major contributor from the CYP subfamily of temazepam production.