Embryo-fetal exposure and developmental outcome of thalidomide following oral and intravaginal administration to pregnant rabbits

- Compared to oral route, intravaginal administration of thalidomide resulted in lower systemic exposures.
- Compared to oral route, intravaginal administration of thalidomide resulted in similar uptake from systemic intrauterine compartment.
- Compared to oral route, intravaginal administration of thalidomide resulted in no difference in embryo-fetal developmental toxicity.

Studies in pregnant rabbits were conducted to evaluate if there are any differences in the uptake of thalidomide into the intrauterine compartment and developmental toxicity risk following oral and intravaginal administration. Thalidomide concentrations in maternal plasma, yolk sac cavity (YSC) fluid and embryo following intravaginal administration were 2- to 7-fold lower than their respective levels after oral administration. Ratios of thalidomide concentration in YSC fluid to maternal plasma were similar between these two routes, indicating no difference in uptake into the intrauterine compartment. A rabbit embryo-fetal development study using oral and intravaginal thalidomide administration at 2 mg/kg/day (a dose >10,000-fold higher than the expected amount of thalidomide in human semen) did not result in any developmental abnormalities. These data demonstrated no preferential transfer mechanism of thalidomide from vagina to conceptus, and no additional embryo-fetal developmental toxicity risks with thalidomide exposure via the vaginal route.