The United States is the world’s leading exporter of pork. In recent years, several of these pork export destination countries have implemented more stringent monitoring protocols for drug residues in meat. In order to maintain a safe, healthy food supply and preserve trade relations, the swine industry must assess the impact of these improved tissue residue testing methods on drug residue detection in meat. This study investigated the residue depletion of flunixin, a commonly used anti-inflammatory drug labeled for use as an adjunctive therapy for swine respiratory disease. This project explored the usefulness of plasma, oral fluid (OF) and urine concentrations of flunixin to predict the residue depletion profile of flunixin in edible tissues of finishing age swine. This project also assessed the potential for untreated pigs to acquire flunixin residues following comingled housing with flunixin treated pigs.
Twenty crossbred finishing pigs were housed in groups of three treated and one untreated control pig. Treated pigs were administered flunixin meglumine at 2.2 mg/kg IM according to product label. Plasma flunixin samples were obtained at 0, 1, 3, 6, 12, 24, 36 and 48 hours after treatment. Necropsy and collection of urine, OF, muscle, liver, kidney, and injection site were conducted at 1, 4, 8, 12, and 16 days post treatment.
A physiologically-based pharmacokinetic (PBPK) model was developed that correlated measured flunixin concentrations in the plasma, OF, urine, liver, kidneys, and muscle. The regression coefficient was R2 = 0.91, suggesting high overall goodness-of-fit. This indicates that the PBPK model could be parameterized with flunixin concentrations in plasma, urine and OF and the results could assist with predicting tissue residues and withdrawal periods in pigs at earlier time points (≤24 h) with a high confidence of accuracy. Thus, OF and urine together with this PBPK model could potentially be a less invasive and more easily administered ante mortem biological monitoring tools for assessing tissue residue potential especially if measured over the first 24 h following flunixin exposure. Although flunixin was not detected in pen-level OF on day 8 post-treatment, OF samples collected at 1, 4 and 12 days after administration were positive for parent flunixin. Furthermore, the 5-hydroxy metabolite of flunixin (5-OH) was present in OF on Day 1, 4, 12 and 16 but not those collected on Day 8. Further studies are needed to refine OF collection for drug analysis.
The potential for environmental residue contamination was also demonstrated in this study. Urine samples from untreated control pigs (no flunixin administration) tested positive for flunixin out to four days post-exposure to flunixin treated pigs. However, flunixin concentrations in the muscle, liver, kidney, and injection sites from these same untreated pigs were below the limit of detection of the assay at all sampling time points after exposure.
With is an increased focus on drug residue concentrations in export markets, often at levels below the tolerance accepted by the USDA FSIS, ante mortem drug monitoring options are needed to ensure pre-harvest food safety. Given the relationship between plasma, urine and oral fluid flunixin concentrations and drug concentrations in body tissue demonstrated in this study, the PBPK model developed as part of this research may be applied as an adjunct to current testing methods. Furthermore, comingling flunixin treated and untreated pigs could result in positive urine tests but does not appear to be a significant risk factor in positive tissue residue tests.