Comparative distribution and metabolism of triamcinolone acetonide and cortisol in the rat embryomaternal unit

Triamcinolone acetonide (TAC) is teratogenic in rats while cortisol has been reported as not teratogenic. The objective of this investigation was to determine whether this difference in teratogenicity could be due to a difference in the metabolism and distribution of the parent compound in the embryomaternal unit. 3H-TAC and 14C-cortisol were administered intramuscularly to pregnant rats on day 12 of gestation. These dams were killed at each of the following time points after injection: 0.5, 1, 3, 6 and 24 hr. Maternal plasma and embryos were analyzed by high performance liquid chromatography (HPLC) and liquid scintillation counting. The plasma concentration of parent TAC was significantly greater than that for parent cortisol at all time points. The plasma elimination half-life for TAC, 86 min, was also calculated to be significantly longer than that for cortisol, 8 min. Furthermore, the percentage of total plasma radioactivity representing HPLC resolved TAC was much higher than that representing cortisol at all time points. The concentration of TAC in the embryos was significantly greater than for cortisol at all time points. The elimination half-life for unchanged TAC in the embryos was 142 min compared to 22 min for cortisol. The percentage of total radioactivity in the embryos representing unchanged TAC was similar to that found in maternal plasma while the percentage of total radioactivity representing unchanged cortisol was much lower than that found in maternal plasma. These findings support the hypothesis that differences in the distribution and metabolism of the parent compound are a critical factor in determining the teratogenicity of that compound.