title: Pharmacokinetics of felbinac after intravenous administration of felbinac trometamol in rats.
abstract: 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. The maximum plasma concentration (C(0)) 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. 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'-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. It would appear that felbinac trometamol has the potential to replace lipid-based NSAID formulations and progress to clinical evaluation.
authors.affiliation: Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiangyong
authors.initials: X
authors.lastname: Cui
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Yantong
authors.initials: Y
authors.lastname: Sun
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
authors.forename: J Paul
authors.initials: JP
authors.lastname: Fawcett
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D010648:Phenylacetates / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014325:Tromethamine / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010648:Phenylacetates; D014325:Tromethamine; C012776:biphenylylacetic acid