Reproductive toxicity studies in rats with rimexolone, a corticoid ophthalmic suspension

Rimexolone is a potent anti-inflammatory corticosteroid with a lower potent ial for elevating intraocular pressure, relative to other ophthalmic steroi ds, and is indicated for postsurgical inflammation and uveitis. Fertility a nd peri/postnatal toxicities were evaluated at oral gavage doses of 50, 150 or 500 mg/kg, and developmental toxicity at 100, 500, or 1000 mg/kg. In th e fertility study, male rats were treated daily beginning 4 weeks prior to mating and females were treated daily beginning 2 weeks prior to mating, an d through gestation day 6. Females were necropsied on gestation day 15 and males were necropsied after 10 weeks of exposure. In males, dose-related re ductions in mean body weights, body weight gains, and food consumption occu rred in all groups. In the 500 mg/kg females, mean body weights were reduce d during gestation, and there was an increase in early resorptions and conc omitant decrease in viable fetuses at this level. There were no effects on copulation or fertility indices, or on the number of corpora lutea and impl antation sites. The no-observed-effect level (NOEL) for fertility and repro ductive effects was 150 mg/kg. In the developmental toxicity study, female rats were treated daily from gestation days 6 through 17, necropsied on ges tation day 20 and fetuses were evaluated. Maternal toxicity occurred at 500 and 1000 mg/kg as indicated by reduced maternal body weights and body weig ht gains. However, there was no indication of a developmental effect on fet uses due to rimexolone. The NOEL was 1000 mg/kg for the developing fetuses. In the peri/postnatal toxicity study, female rats were treated daily from gestation day 6 through lactation day 20 and necropsied. Fl developmental a nd behavioral parameters were evaluated. Selected Fl animals were mated at 12 weeks, allowed to deliver, and necropsied on lactation day 21. At 500 mg /kg, F0 maternal body weights were reduced during gestation and lactation, and Fl pup weights were reduced during lactation and the growth phase. Ther e were no effects on the F1 fertility or reproductive capabilities, or on F 2 developmental parameters. The NOEL for the F0 females and F1 offspring wa s 150 mg/kg. Together, these studies indicate that, unlike some corticoster oids, rimexolone does not produce developmental or reproductive toxicity in rats.