1999 Volume 14 Issue 1 Pages 32-41
The absorption, distribution and metabolism of bromfenac sodium were investigated after single or repeated application of 14C-bromfenac sodium ophthalmic solution to both eyes of male albino rabbits at a dose of 0.1 mg/animal (0.05 mg/50 μl/eye).
1. After single instillation, plasma level of radioactivity reached a maximum of 113.2 ng eq./ml at 30 min and then declined with a half-life of 2.2 hr from 1 hr to 12 hr. The radioactivity levels, in almost half of the ocular tissues, reached the maxima at 30 min after administration. Radioactivity distribution to the corneas was the highest, followed by the anterior sclera and conjunctiva. Radioactivity levels in the lens and vitreous body were the lowest. At 72 hr after administration, radioactivity level in the lens was 7% of the maximum but radioactivity in the other tissues was below the detection limit.
2. During repeated instillation, radioactivity level in plasma was below the detection limit at 24 hr after a single dose, but increased with the number of doses after 7 doses and then reached a steady state by 21 doses. Radioactivity levels in ocular tissues increased with the number of doses except a part of tissues, but then reached a steady state by 21 doses. Radioactivity levels in the lens and posterior sclera after 21 doses were 4.0 and 1.6 times higher than those after a single dose, respectively. Elimination of radioactivity from the plasma and ocular tissues after 21 doses was slightly slower than that after a single dose.
3. Parent compound in the aqueous humor collected at 1, 2 and 4 hr after single instillation accounted for 73.0-79.5% of radioactivity in aqueous humor. Four metabolites, a benzoic acid derivative AHR-11665, formed by oxidation of the carboxymethyl group of bromfenac, its precursor WAY-127039-A-1, and 2-oxyindole derivative AHR-10240 and isatine derivative AHR-11652 formed by intramolecular cyclization were detected. Parent compound in the plasma accounted for 76.7-80.5% of radioactivity in plasma at 1, 2 and 4 hr after single instillation. Unknown metabolites 1RaP1, 1RaP2 and 1RaP3 were detected in addition to the metabolites detected in the aqueous humor.
