Pharmacokinetics of triflusal and its main metabolite in rats and dogs

Abstract

The methods for determining plasma concentrations of triflusal (2-acetoxy-4-trifluoromethyl benzoic acid) that have been described, do not distinguish between the drug and its main metabolite HTB (2-hydroxy-4-trifluoromethyl benzoic acid). In the present study, we have developed a new analytical technique based on HPLC that enabled us to carry out a pharmacokinetic study of the drug and its metabolite in animals. An intravenous or oral dose of 50 mg/kg was administered to male Sprague-Dawley rats, and 15 mg/kg was administered to beagle dogs. Plasma levels of triflusal and HTB were determined. In rats, triflusal was quickly eliminated from plasma with a biological half-life (t1/2) of 2.7 min and a clearance (Cl) of 73.4 (ml/kg)/min. The elimination of HTB was much slower with a t1/2 of 21.5 h and a Cl of 5.1 (mg/kg)/h. The maximum concentration (Cmax) of triflusal in rats after an oral administration was 8.1 +/- 2.0 micrograms/ml reached between 2.5 and 10 min. The Cmax of HTB was 237.7 micrograms/ml and was achieved at 0.7 h. The bioavailability of triflusal in rats was only 10.6% while the bioavailability of HTB was more than 100% indicating an important first pass effect. In dogs the t1/2 of triflusal was 14.4 +/- 5.9 min and the Cl was 25.1 +/- 4.7 (ml/kg)/min. HTB was also eliminated very slowly with a t1/2 of 71.1 +/- 12.5 h and a Cl of 2.4 +/- 0.3 (ml/kg)/h. The Cmax of triflusal in dogs was 13.3 +/- 2.9 micrograms/ml and was reached after 19.2 +/- 6.1 min (tmax).(ABSTRACT TRUNCATED AT 250 WORDS)