PHARMACOKINETICS AND PHARMACODYNAMICS OF TOLFENAMIC ACID IN CALVES

Pharmacokinetic/pharmacodynamic modelling was applied to a study in wh ich tolfenamic acid was administered intravenously to calves at a dose rate of 2 mg kg(-1). The drug had a shorter mean (SEM) elimination ha lf-life (T1/2 beta) of 2.5 (0.95) hours and a larger volume of distrib ution (Vd(area)) of 0.98 (0.28) litre kg(-1) than other non-steroidal anti-inflammatory drugs. Its body clearance was high with a mean value of 0.30 (0.06) litre kg(-1) h(-1). It had inhibitory effects on infla mmatory exudate PGE(2) and beta-glucuronidase, serum TxB(2) and bradyk inin-induced swelling but it did not affect exudate LTB(4) concentrati ons. fts mean EC(50) values were lower for exudate PGE(2), beta-glucur onidase and bradykinin-induced swelling inhibition (0.077 [0.018]; 0.0 40 [0.017] and 0.030 [0.020] mu g ml(-1), respectively) than for serum TxB(2) inhibition (0.137 [0.079) mu g ml(-1)). Then were also differe nces in its equilibration half-life, which was short for the inhibitio n of serum TxB(2), intermediate for exudate PGE(2) and beta-glucuronid ase acid longer for bradykinin-induced swelling. These differences may be explained by the existence of three distribution compartments rela ting to the different sites of action of the drug.