The fate of [14C]thalidomide in the pregnant hamster

Abstract

Abstract The embryotoxicity and fate of [14C]thalidomide in the pregnant European golden hamster have been investigated. Daily administration of thalidomide (1 or 2 g/kg orally) to pregnant hamsters on days 4–12 inclusive of pregnancy was not embryotoxic. [14C]Thalidomide (150 mg/kg) administered on the 204th hr of pregnancy is well absorbed and about 84% of the 14C is excreted in the urine and 9% in the faeces in the 3 days after dosing. The urinary 14C consists of thalidomide (3% of dose), α-(o-carboxybenzamido)glutarimide (26%), 2- and 4-phthalimidoglutaramic acids (8%), 2-phthalimidoglutaric acid (0.2%) and 2- and 4-(o-carboxybenzamido)-glutaramic acids plus 2-(o-carboxybenzamido)glutaric acid (27%). 14C is present in the embryo and the relative concentrations of radioactivity in the embryo and plasma are about the same at 4, 12 and 24 hr after dosing. At 4 hr after dosing the embryo contains mainly thalidomide, but at 12 hr this has largely disappeared and the 14C consists of seven hydrolysis products. The lack of embryotoxicity of thalidomide in the hamster is thus not due to an inability of the teratogen to penetrate to the conceptus.