The metabolism of radiolabeled cortisol and triamcinolone acetonide (TAC) was compared in the early, middle, and late gestational age rhesus monkeys. Trace amounts of 14C-cortisol and 10 mg/kg 3H-TAC (Kenalog®) were simultaneously administered i.m. to the maternal animal. Whole 30-day embryos or 61 - to 137-day fetal organs, amniotic fluid, and placenta were collected from 0.5 to 24 h after dose administration and analyzed by high-performance liquid chromatography (HPLC). Serial blood samples collected from all maternal animals and the late gestational age fetuses were similarly processed. The maternal plasma concentration of total radioactivity derived from TAC 1-60 min after dose administration was significantly less on day 30 of gestation as compared to day 60 at the 5-, 10-, and 60-min time points. At 60 and 130 days of gestation, however, the maternal plasma concentrations of total radioactivity were similar. Concentrations of cortisol-derived radioactivity in the maternal plasma were the same across gestational age. The plasma TAC and cortisol metabolic profiles, as determined by HPLC, were not significantly different throughout pregnancy. In late pregnancy 30 min after dose administration, the fetal to maternal plasma cortisol ratio was 0.34, whereas the same ratio for TAC was 0.96. By 1 h after dose administration, less than 8% of the total l4C radioactivity in fetal tissues was cortisol and over 92% of the 3H was TAC. The extensive fetoplacental metabolism of cortisol to inactive metabolites and the resistance of TAC to metabolic conversion results in greater TAC than cortisol exposure of the developing rhesus monkey conceptus.

Keywords:
Rhesus monkey, Cortisol, Triamcinolone acetonide, Placental transfer, Glucocorticoid metabolism
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1984
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