The Effect of Breed and Sex on Drug Depletion and Differential Gene Expression Associated with Drug Metabolism after Fenbendazole and Flunixin Administration

Drug use in animal agriculture has received increased attention due to welfare concerns, food safety, and drug resistance. Characterizing heterogeneity in the way swine populations respond to drugs at the phenotypic and molecular level allows for group specific dose or drug recommendations. Our objective was to determine if drug depletion differs across breed and gender for Sulfamethazine, Enrofloxacin , Fenbendazole (FBZ) and Flunixin (FLU) and to determine if genes associated with drug metabolism are differentially expressed across breed and gender for FBZ and FLU. For the initial analysis, 8 sires derived from four breeds, Duroc, Hampshire, Landrace, or Yorkshire, were mated to a common sow population generating 114 pigs. A random crossover design was utilized and drugs were administered intravenously. Blood was collected a minimum of 10 times over 48 hours. Pharmacokinetics parameters (PK) derived from a non-compartmental analysis of drug and metabolite plasma concentration vs. time profiles were analyzed using linear models within each drug and across all drugs. Following the initial analysis, 32 additional pigs, equally split by breed and sex, were utilized to collect liver samples after administration of either FBZ or FLU. Quantitative real-time PCR was used to measure gene expression levels. The PK analysis within each drug revealed breed differences for FLU (P-value<0.05) and FBZ (P-value<0.05) and sex differences for FBZ (P-value<0.05). It has been shown that drug depletion differs across breed and gender. Results pertaining to the identification of differential expressed genes associated with drug metabolism will be forthcoming.