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)

Administration, Oral↗

PubMedDate not supplied

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

The pharmacokinetic profile of triflusal (2-acetoxy-4-trifluoromethyl benzoic acid) and its main metabolite HTB (2-hydroxy-4-trifluoromethyl benzoic acid) has been studied in 8 healthy subjects (4 males and 4 females), after a single oral dose of 900 mg of triflusal. Plasma concentrations were determined by a sensitive HPLC method. Sampling was performed up to 120 h post medication. Triflusal displays a Cmax of 11.6 +/- 1.7 micrograms/ml and a tmax of 0.88 +/- 0.26 h. The elimination half-life (t1/2) was 0.55 h with a clearance (Cl/F) of 45.5 +/- 11.0 l/h. HTB kinetic parameters were: tmax 4.96 +/- 1.37 h and Cmax 92.7 +/- 17.1 micrograms/ml, with an elimination t1/2 of 34.3 +/- 5.3 and a clearance of 0.18 +/- 0.04 l/h. The results obtained in this study show a rapid absorption of triflusal and an immediate biotransformation into HTB. The long lasting platelet anti-aggregatory effect of triflusal in spite of its short t1/2, could be explained by the irreversible inhibition of platelet cyclo-oxygenase and the sustained levels of HTB, which also possess anti-aggregant properties.

Administration, Oral↗

PubMedDate not supplied

Flutrimazole 1% dermal cream in the treatment of dermatomycoses: a randomized, multicentre, double-blind, comparative clinical trial with 1% clotrimazole cream. Flutrimazole Study Group.

In a multicentre, double-blind, randomized, parallel group clinical trial, the efficacy and tolerability of flutrimazole 1% dermal cream were compared with those of a reference compound, clotrimazole 1% dermal cream, applied topically twice daily for 4 weeks in patients with clinically and mycologically diagnosed fungal infection of the skin. A total of 484 patients were included in the study (244 patients received flutrimazole cream and 240 clotrimazole cream). According to an intention to treat analysis of the data, there was no difference between the treatments in terms of the rate of mycological cure after 4 weeks: 79% of patients in the clotrimazole group and 80% of patients in the flutrimazole group were mycologically cured (P = 0.83). From a safety point of view, flutrimazole and clotrimazole were well tolerated and the overall incidence of adverse reactions (mainly mild local reactions such as irritation or burning sensation) was 7%. This study shows that, in the treatment of fungal infections of the skin, topically applied flutrimazole has good efficacy, similar to that of clotrimazole, and is well tolerated.

Administration, Topical↗