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)

Pharmacokinetics of triflusal and its main metabolite HTB in healthy subjects following a single oral dose

“…There is a large difference between the elimination half-life (tI/2) of triflusal and HTB, both in rat and dog. The tl/2 of triflusal is a few minutes while that of HTB is hours or even days in both species (13).…”

“…Absolute bioavailability in dogs was 83% while in rats it was only 15% (13). Nevertheless, when bioavailability is expressed in terms of taking HTB values it was 89% in dogs and over 100% in rats (13,15).…”

Triflusal: An Antiplatelet Drug with a Neuroprotective Effect?

“…in healthy humans was found to be 0.5 ± 0.1 h, while the half-life of HTB was 34.3 ± 5.3 h. The C max was 11.6 ± 1.6 ìg/mL for triflusal and 92.7 ± 17.1 ìg/mL for HTB, renal clearance was 0.8 ± 0.2 L/h for triflusal and 0.18 ± 0.04 L/h for HTB, and T max was 0.88 ± 0.26 h for triflusal and 4.96 ± 1.37 h for HTB. At 4 h after oral administration, plasma levels of triflusal were undetectable (47)(48)(49). These values illustrate the difference in plasma half-life between triflusal (slightly longer than 30 min) and HTB (nearly 35 h).…”

“…In animals its excretion is mainly renal, with a urinary clearance of 60% at 48 h after intake (43,44,49,52). In urine, free HTB, glycine-conjugated HTB, and an unidentified metabolite with greater polarity than HTB (52) have been identified in addition to unchanged triflusal.…”

Effects of Triflusal and Aspirin in a Rat Model of Cerebral Ischemia

“…Each group received the same drug treatment for 2 additional days. Details on the pharmacokinetics of triflusal can be found in Ramis et al 10 Benzathine penicillin G was given as prophylactic antibiotic. After wound suture, all rats received 40 mg/kg of buprenorphine intramuscularly and were allowed to recover from surgery for 3 days.…”