Pharmacokinetics and pharmacodynamics of tolfenamic acid in calves

Pharmacokinetic/pharmacodynamic modelling was applied to a study in which tolfenamic acid was administered intravenously to calves at a dose rate of 2 mg kg(-1). The drug had a shorter mean (SEM) elimination half-life (T1/2 beta) of 2.5 (0.95) hours and a larger volume of distribution (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 inflammatory exudate PGE(2) and beta-glucuronidase, serum TxB(2) and bradykinin-induced swelling but it did not affect exudate LTB(4) concentrations. fts mean EC(50) values were lower for exudate PGE(2), beta-glucuronidase and bradykinin-induced swelling inhibition (0.077 [0.018]; 0.040 [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 differences in its equilibration half-life, which was short for the inhibition of serum TxB(2), intermediate for exudate PGE(2) and beta-glucuronidase acid longer for bradykinin-induced swelling. These differences may be explained by the existence of three distribution compartments relating to the different sites of action of the drug.