Nonsteroidal anti-inflammatory agents: species differences in pharmacodynamics.

Abstract

The disposition kinetics and systemic availability of nonsteroidal anti-inflammatory (NSAI) agents as well as their antipyretic and anti-nociceptive properties are reviewed in different species. The anti-inflammatory versus bradykinin, serotonin and kaolin oedema activities of aspirin (ASA), phenylbutazone (PBZ) and indomethacin (IDM) explain their large use in veterinary medicine. The low analgesic effect versus NO3Ag arthritis, radiant heat and tail pressure of indomethacin and oxyphenbutazone contrasts with the widespread activity of phenazone. The comparative inhibitory effect of NSAI agents on the rat fundus contraction due to arachidonic acid is an indication of their relative inhibition of prostaglandin biosynthesis. Among the side-effects of NSAI agents, the long-lasting hyperactivity and hypomotility induced by a parenteral injection of phenylbutazone in the dog is of importance despite the fact that in this species, as in the horse, the average half life is only 6 h due to side-chain hydroxylation (versus 42 h in man for whom conjugation is a major pathway). Initiation of therapy with a loading dose followed by maintenance doses (each half the size of the loading dose) at constant intervals equal to the half-life of the drug has been shown to be suitable for most drugs with long half-life values. According to this a tentative harmless dosage regimen can be calculated for NSAI therapy in different species.