PHARMACOKINETICS OF FLUNIXIN MEGLUMINE IN BEEF CATTLE AFTER SUBCUTANEOUS AND INTRAMUSCULAR ADMINISTRATION
Animal Metabolism-Agricultural Chemicals Research
2012 Annual Report
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.
Perfluorooctane sulfonate (PFOS) is a household and industrial surfactant that has been implicated as a contaminant of some pastureland amended with municipal waste products. Very few data are available on the rates of PFOS absorption and excretion in cattle, even though cattle have been shown to graze on contaminated land. Therefore, several cattle were orally dosed with PFOS and serial blood samples were removed for a 12 month period; some cattle were slaughtered at selected time intervals in order to measure tissue residues of PFOS. The live phase of the study is completed and the analytical phase is in progress. Rates of PFOS depuration from blood and edible tissues will be estimated upon completion of the analytical phase of the study.