Pharmacokinetics and pharmacodynamics of tolfenamic acid in calves

Abstract

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 ( T 1 2β ) 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 β-glucuronidase, serum txb 2 and bradykinin-induced swelling but it did not affect exudate ltb 4 concentrations. Its mean ec 50 values were lower for exudate pge 2, β-glucuronidase and bradykinin-induced swelling inhibition (0·077 [0·018]; 0·040 [0·017] and 0·030 [0·020] μg ml −1, respectively) than for serum txb 2 inhibition (0·137 [0·079) μg ml −1). There were also differences in its equilibration half-life, which was short for the inhibition of serum txb 2, intermediate for exudate pge 2 and β-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.