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.
Ramis
J
J
Research Center, J. Uriach & Cia S.A., Barcelona, Spain.
Mis
R
R
Forn
J
J
Torrent
J
J
Gorina
E
E
Jané
F
F
D000284:Administration, Oral; D000328:Adult; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012459:Salicylates / Q000008:administration & dosage / Q000493:pharmacokinetics*
D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; C016167:triflusal; C033502:4-trifluoromethylsalicylic acid