COMPARATIVE PHARMACODYNAMICS OF FLUNIXIN, KETOPROFEN AND TOLFENAMIC ACID IN CALVES

The pharmacodynamics of the non-steroidal anti-inflammatory drugs flunixin, tolfenamic acid and ketoprofen were studied in calves after intravenous administration, An acute inflammatory reaction was induced in tissue cages by the intracaveal injection of the mild irritant carrageenan, and the inhibition of inflammatory mediators and enzymes was investigated. The substances measured in the exudate included the enzymes (active and total metalloproteases, serine and cysteine proteases, acid phosphatase [AP], lactate dehydrogenase [LDH] and beta-glucuronidase) and the eicosanoids (prostaglandin [PG]E(2) and leukotriene [LT]B-4). Studies were also made of inhibition of the synthesis of serum thromboxane (Tx)B-2 ex vivo, of bradykinin-induced oedema in vivo and of the generation of superoxide anions (O-2(-)) in vitro. None of the drugs affected the concentration of LTB(4), Or the activities of metalloproteases, cysteine and serine proteases, AP or LDH in the exudate. All the drugs inhibited the synthesis of serum TxB(2) and exudate PGE(2) and inhibited the release of beta-glucuronidase, They also decreased the oedematous response to intradermally injected bradykinin and inhibited the generation of O-2(-) ions by neutrophils in vitro. These actions may contribute to the anti-inflammatory effects of the drugs and hence to their clinical efficacy.