Effects of Breed and Sex on Liver Gene Expression and Pharmacokinetic Parameters in Pigs

Drug use in animal agriculture has received increased attention due to welfare concerns, food safety and drug resistance. Characterizing heterogeneity in how pig populations respond to drugs at the phenotypic and molecular levels allows for group-specific dose or drug recommendations. Our objective was to determine if drug depletion differs across breed and gender for four FDA-approved swine medications and to determine if genes associated with drug metabolism are differentially expressed across breed and gender. For the initial drug evaluation, eight sires derived from four breeds, Duroc, Hampshire, Landrace and 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 ten times over 48 hours. Pharmacokinetics parameters 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. Results from the initial study indicated that two of the four drugs had drug depletion curves that differed across breed and/or gender. Following the initial analysis, 32 additional pigs, equally split by breed and sex, were utilized to collect liver samples after administration of one of the two selected drugs. Quantitative real-time PCR are being used to measure gene expression levels and results will be discussed.