Pharmacokinetics of felbinac after intravenous administration of felbinac trometamol in rats

Abstract

1. Felbinac trometamol (trishydroxymethylaminomethane 4-biphenylacetate) is a new water-soluble salt of felbinac currently undergoing clinical evaluation as an intravenous (i.v.) formulation for the treatment of severe post-operative pain. This article reports the pharmacokinetics of felbinac after i.v. administration of felbinac trometamol in Sprague–Dawley rats.

2. The maximum plasma concentration (C₀) and area under the plasma concentration-time curve (AUC) of felbinac administered at doses of 3.36, 8.40 and 21.0 mg/kg felbinac trometamol increased linearly with dose.

3. Felbinac was highly protein bound (~95%) at plasma concentrations up to 75 μg/ml and extensively metabolized with only small amounts being excreted unchanged in urine (0.318%), feces (0.530%) and bile (0.465%).

4. 4′-Hydroxyfelbinac was the principal metabolite in urine, feces and bile together with felbinac glucuronide, 4′-hydroxyfelbinac glucuronide and sulfate. The majority of the administered dose was excreted in urine (63.6%) mostly as 4′-hydroxyfelbinac. Total drug in urine and feces accounted for about 72% of the dose.

5. It would appear that felbinac trometamol has the potential to replace lipid-based NSAID formulations and progress to clinical evaluation.

Keywords::

• Metabolism
• LC-MS/MS
• excretion
• protein binding

Acknowledgements

This project was supported by the National Major Special Project for Science and Technology Development of the Ministry of Science and Technology, P.R. China (2009ZX09304-003), the Innovation Fund for Small Technology-based Firms and the Ministry of Science and Technology, P.R. China (08C26214401254).

Declaration of interest

The authors report no declarations of interest.