Studies on Intravenously Infused Dexamethasone in Sheep

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Abstract
The metabolism of [1,2(n)-3H]dexamethasone infused i.v. for periods of 4 and 8 days was examined in 4 Merino wethers. On average 85.6 .+-. 2.8 (s.e.m. [standard error of the mean]) % of the total dose was recovered, 56.2 .+-. 5.1 and 29.4 .+-. 3.3% being excreted in urine and feces, respectively. In total, 12.4% of the dose was associated with the unconjugated steroid fraction which represented 22% of the total urinary radioactivity. TLC of the urinary unconjugated fraction revealed, apart from dexamethasone, 5 major and 3 minor radioactive components designated as I, III, IV, V, VIII and II, VII, IX respectively. Approximately 83% of the radioactivity associated with the unconjugated fractions was found in constituents more polar than dexamethasone with the radioactivity mainly confined to the principal metabolite IV, Rf = 0.24 (dexamethasone, Rf = 0.45; chloroform:formamide 50:1). The urinary constituent VI, Rf = 0.37, was detected only during the 2nd half of the 8-day infusion with the peak of excretion on day 6. During the 1st 30 h of [3H]dexamethasone administration the plasma radioactivity reached the level which remained relatively constant throughout the infusions. The initial high level of radioactivity detected in the plasma unconjugated fraction as well as dexamethasone during the 1st 24 h infusion declined over the next 2 days; this was followed by a small increase during the final period of infusions. The radioactivity of the plasma unconjugated fraction was distributed, apart from dexamethasone, into 6 constituents (I, III, IV, V, VIII and IX) which when analyzed by TLC appeared to be qualitatively similar to those found in urine. One or more products of dexamethasone metabolism might be biologically active and thus potentially important in inhibiting wool fiber growth in sheep.