1a. Objectives (from AD-416)
Flunixin is a potent and effective non-steroidal anti-inflammatory agent that is labeled for use in cattle only after intravenous (IV) administration. Unfortunately, IV administration is difficult and time consuming in cattle, and it is almost never done in the field, instead flunixin is usually dosed by intramuscular (IM) or subcutaneous administration (SC). The practice of IM and SC flunixin administration in cattle is thought to contribute to the increasing numbers of violative residues found in edible tissues of beef cattle, because the release and elimination of flunixin from fascia and muscle is believed to be delayed after IM and SC dosing. Several studies have been published on the pharmacokinetics of flunixin after IV dosing, but studies on the pharmacokinetics after SC or IM dosing in beef cattle are lacking. Thus, the objective of this project is to determine the pharmacokinetics of flunixin meglumine in serum of beef cattle after extra-label administration. Results will provide an insight in to the longevity of flunixin in tissues after exra-label administration.
1b. Approach (from AD-416)
Ten growing cattle will be purchased and used in a crossover study. In period 1, five cattle will be dosed with flunixin meglumine via SC administration and five cattle will be dosed with flunixin via IM administration. Blood will be collected, and serum prepared, from each animal approximately 23 times over the course of a 9-day period. A minimal 7-day washout period will allow any drug residue to deplete from animals and period 2 will be conducted. In period 2, dosing routes will be switched, and each animal will either a SC or IM dose of flunixin so that each animal will be exposed to each route of dosing. Serum samples will be prepared and analyzed for flunixin by immunoassay and liquid chromatography mass spectrometry.
3. Progress Report
The live phase of a study was completed in which five steers and five heifers were dosed with flunixin meglumine in a cross-over design via intravenous and subcutaneous administration. The cooperating parties agreed that the intramuscular route of administration, shown in the agreement title, would be dropped in favor of intravenous administration. Serial blood samples were collected from dosed animals and flunixin content was determined via immunochemical analyses. Blood concentration data vs. time were plotted so that the blood depletion of flunixin could be described using mathematical models. The same samples will be assayed using liquid chromatography-mass spectrometry and the two methods compared. In addition, kinetic data will be compared between the two routes of administration and the data used to predict safe withdrawal times after subcutaneous dosing. Manuscripts have not yet been prepared describing and interpreting data derived from the study, but cooperators are planning on completing a manuscript in the coming year. ADODR monitoring of the project is done via phone calls, e-mails, discussions at professional meetings, and on-site visits.