Pharmacokinetics of Intravenous, Intramuscular, Oral, and Transdermal Administration of Flunixin Meglumine in Pre-wean Piglets

Castration and tail-docking of pre-wean piglets are common procedures that are known to induce pain and would benefit from pain mitigation. Flunixin meglumine (FM) is a non-steroidal anti-inflammatory drug currently approved in the United States for pyrexia in swine and lameness pain in cattle. The objective of this study was to establish the pharmacokinetic (PK) parameters resulting from intravenous (IV), intramuscular (IM), oral (PO) and transdermal (TD) administration of FM in pre-wean piglets. FM was administered to thirty-nine pre-wean piglets at a target dose of 2.2 mg/kg for IV and IM and 3.3 mg/kg for PO and TD route. Plasma was collected at twenty-seven time points from 0 to 9 days after FM administration and concentrations were determined using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Pharmacokinetic data were analyzed using noncompartmental analysis (NCA) methods and nonlinear mixed-effects (NLME). Initial plasma concentration for IV (C(0)) 11,653 μg/L and mean peak plasma concentrations (C(max)) 6,543 μg/L (IM), 4,883 μg/L (PO), and 31.5 μg/L (TD) were measured. The time points of peak FM concentrations (t(max)) were estimated 30 min, 1 h, and 24 h for IM, PO, and TD, respectively. The bioavailability (F) of PO and IM FM was estimated at >99%, while the bioavailability of TD FM was estimated to be 7.8%. The reported C(max) of FM after IM and PO administration is consistent with therapeutic concentration ranges that mitigate pain in other species and adult pigs. However, the low estimated concentration of FM after TD dosing is not expected to mitigate pain in pre-wean piglets. The low F of TD FM suggests that expanding the surface area of application is unlikely to be sufficient to establish an effective TD dose for pain, while the high bioavailability for PO FM should allow for an effective dose regimen to be established.