ウサギ精漿を介したサリドマイドによる発生毒性のリスク

抄録

The use of contraception for men taking pharmaceuticals has been regulated on safer side due to the damage caused by thalidomide. However, this regulation should be based on evidence. We examined the risk of seminal plasma-mediated developmental toxicity with thalidomide in rabbits, which are susceptible to teratogenicity from thalidomide. After oral administration in male rabbits, thalidomide was transferred to the seminal plasma in the same or slightly lesser amount as plasma. When thalidomide at approximately 100 times the maximum plasma transfer concentration was administered intravaginally to pregnant rabbits on gestational days 1 to 13, the fetuses showed no teratogenic effects. The pharmacokinetics results after oral administration were approximately 2500-fold higher for Cmax and 4900-fold higher for AUC_0-t than those of the vaginal administration study. However, the dose difference between the two administration methods was 625 folds, indicating that maternal exposure through semen was minimal and the risk of teratogenic expression was low. In this symposium, possible of teratogenic effects via seminal plasma from our thalidomide experiments in rabbits will be discussed, considering species differences.