Pharmacokinetics, Safety and Tolerability of Triflusal and its Main Active Metabolite HTB in Healthy Chinese Subjects

Abstract

Objective:

Triflusal presents comparable antiplatelet activity to aspirin while presenting a more favourable safety profile, and is used in the treatment of thrombosis. The study aimed to evaluate the pharmacokinetics and safety of triflusal and its major metabolite 2-(hydroxyl)-4-(trifluoromethyl)- benzoic acid (HTB) in healthy Chinese subjects.

Methods:

30 healthy subjects were recruited in this randomized, single-center, and open-label, parallel, single ascending doses (300, 600, 900 mg) and multiple doses (600 mg, once daily for 7 days) study. Plasma samples were analyzed with a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) method. Safety was assessed by adverse events, ECG, laboratory testing, and vital signs.

Results:

Triflusal was safe and well tolerated. After single-dose administration, triflusal was rapidly absorbed with a mean T_max of 0.55–0.92 h and a mean t_{1/2 kel} of 0.35–0.65 h, HTB was absorbed with a mean T_max of 2.35–3.03 h and a mean t_{1/2 kel} of 52.5–65.57 h. C_max and AUC for triflusal and HTB were approximately dose proportional over the 300–900 mg dose range. In the steady state, the accumulation index (R) indicated that the exposure of triflusal increased slightly with repeated dosing, and the exposure of HTB increased obviously. 3 adverse events certainly related to the investigational drugs occurred in the multiple-dose phase.

Conclusion:

Following oral dosing under fasting condition, triflusal is promptly absorbed and rapidly depleted from the systemic circulation. HTB is quickly generated from triflusal and slowly eliminated. Triflusal accumulates slightly in the body. HTB plasma concentration builds up progressively toward steady-state.

Key words

triflusal - pharmacokinetics - antiplatelet activity - safety

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