COMPARATIVE PHARMACODYNAMICS OF FLUNIXIN, KETOPROFEN AND TOLFENAMIC ACID IN CALVES

The pharmacodynamics of the non-steroidal anti-inflammatory drugs flun ixin, tolfenamic acid and ketoprofen were studied in calves after intr avenous administration, An acute inflammatory reaction was induced in tissue cages by the intracaveal injection of the mild irritant carrage enan, and the inhibition of inflammatory mediators and enzymes was inv estigated. The substances measured in the exudate included the enzymes (active and total metalloproteases, serine and cysteine proteases, ac id phosphatase [AP], lactate dehydrogenase [LDH] and beta-glucuronidas e) and the eicosanoids (prostaglandin [PG]E(2) and leukotriene [LT]B-4 ). Studies were also made of inhibition of the synthesis of serum thro mboxane (Tx)B-2 ex vivo, of bradykinin-induced oedema in vivo and of t he generation of superoxide anions (O-2(-)) in vitro. None of the drug s affected the concentration of LTB(4), Or the activities of metallopr oteases, cysteine and serine proteases, AP or LDH in the exudate. All the drugs inhibited the synthesis of serum TxB(2) and exudate PGE(2) a nd inhibited the release of beta-glucuronidase, They also decreased th e oedematous response to intradermally injected bradykinin and inhibit ed the generation of O-2(-) ions by neutrophils in vitro. These action s may contribute to the anti-inflammatory effects of the drugs and hen ce to their clinical efficacy.