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 (Vdarea) 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 PGE2 and beta-glucuronidase, serum TxB2 and bradykinin-induced swelling but it did not affect exudate LTB4 concentrations. Its mean EC50 values were lower for exudate PGE2, beta-glucuronidase and bradykinin-induced swelling inhibition (0.077 [0.018]; 0.040 [0.017] and 0.030 [0.020] microgram ml-1, respectively) than for serum TxB2 inhibition (0.137 (0.079) microgram ml-1). There were also differences in its equilibration halflife, which was short for the inhibition of serum TxB2, intermediate for exudate PGE2 and beta-glucuronidase and 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.