The Disposition and Metabolism of Flurbiprofen in Several Species Including Man

Abstract

Flurbiprofen was rapidly absorbed in all species studied.

2. Half-lives of elimination measured 0 to 12 h after a single dose were: mouse 3·4 h, rat 2·5 h, dog 10·1 h, baboon 3·1 h and man 3·9 h. A second phase of elimination was seen in the dog. Flurbiprofen accumulated in the circulation of the dog on repeated dosing.

3. After dosing with [¹⁴C]flurbiprofen, tissue levels of radioactivity in dog and baboon were similar to that in plasma. In the rat, levels were slightly elevated in liver, kidney, large intestine and thyroid after repeated dosing.

4. The dog excreted equal amounts of radioactivity in urine and faeces. In other species renal excretion was the more important route.

5. Six metabolites have been detected, the most important being: 2-(2-fluoro-4′-hydroxy-4-biphenylyl)propionic acid (metabolite 1), 2-(2-fluoro-3′,4′-dihydroxy-4-biphenylyl)propionic acid (metabolite 2) and 2-(2-fluoro-3′-hydroxy-4′-methoxy-4-biphenylyl)propionic acid (metabolite 3). The proportions of the metabolites and the extents of their conjugation varied among the species.

6. Metabolites were detected in the circulation of rat, mouse and baboon but not in dog and man.

7. Flurbiprofen did not affect the hepatic drug-metabolizing enzyme system of rat.

8. Flurbiprofen was extensively bound to serum protein of rat, dog, baboon and man.