Rowland J M, Althaus Z R, Slikker W, Hendrickx A G
Toxicol Appl Pharmacol. 1983 Jan;67(1):70-7. doi: 10.1016/0041-008x(83)90245-4.
The distribution and metabolism of triamcinolone acetonide (TAC) in the rat embryomaternal unit were investigated during a teratogenically sensitive period. Pregnant rats (Day 12 of gestation) were injected im with 0.125 or 0.5 mg/kg [3H]TAC. Maternal plasma and embryos were collected at selected time points and analyzed by HPLC and liquid scintillation counting. No significant differences in the percentage of total radioactivity representing unchanged TAC, concentration of TAC, or its elimination half-life were detected in either plasma or embryos of the two dose groups. These results provide evidence that the metabolism and distribution of TAC in the rat embryomaternal unit are dose independent over this known teratogenic dose range. To determine whether multiple administration of TAC resulted in any alterations in maternal or embryonal exposure, the same parameters were evaluated following one (Day 12), two (Days 12 and 13), or three (Days 12, 13, and 14) injections of [3H]TAC (0.5 mg/kg, im). The only alterations detected were an increase in the percentage of total radioactivity in maternal plasma representing unchanged TAC at 1 hr following the second or third injection and an increase in the embryonal concentration of TAC at the same time points.
在致畸敏感期研究了曲安奈德(TAC)在大鼠胚胎-母体单位中的分布和代谢。妊娠大鼠(妊娠第12天)腹腔注射0.125或0.5mg/kg [³H]TAC。在选定时间点收集母体血浆和胚胎,并通过高效液相色谱法和液体闪烁计数法进行分析。在两个剂量组的血浆或胚胎中,未检测到代表未变化TAC的总放射性百分比、TAC浓度或其消除半衰期的显著差异。这些结果证明,在这个已知的致畸剂量范围内,TAC在大鼠胚胎-母体单位中的代谢和分布与剂量无关。为了确定多次给予TAC是否会导致母体或胚胎暴露的任何改变,在单次(第12天)、两次(第12天和第13天)或三次(第12天、第13天和第14天)注射[³H]TAC(0.5mg/kg,腹腔注射)后,对相同参数进行了评估。检测到的唯一改变是在第二次或第三次注射后1小时,母体血浆中代表未变化TAC的总放射性百分比增加,以及在相同时间点胚胎中TAC浓度增加。