Distribution and metabolism of triamcinolone acetonide in mice sensitive to its teratogenic effects

Since glucocorticoids cause a high frequency of cleft palate in the A/J mouse strain the distribution of labeled triamcinolone acetonide and the presence of its metabolites in embryos and pregnant females were investigated. 3 H‐Triamcmolone acetonide (5 mg/kg) was primarily excreted by the females through the enterohepatic circulation. Organic‐solvent extraction and subsequent thin‐layer chromatography revealed at least six metabolites, plus 38‐50% of unmetabolized drug, in maternal liver; however, only about 9% of unmetabolized steroid was present in bile. After 0.5 hr of administration of a dose of labeled triamcinolone acetonide causing 100% cleft palate practically all the radioactivity in embryos and placentas was unmetabolized drug, embryo concentration being 1 × 10 −6 M. Thereafter, the concentration of drug in embryos and placentas fell markedly. It is concluded that triamcinolone acetonide and not its metabolites is the teratogenic agent.