Metabolism of Triamcinolone Acetonide-21 -phosphate in Dogs, Monkeys, and Rats

Abstract

The absorption, distribution, and metabolic fate of triamcinolone acetonide-14C-21-phosphate were studied in the dog, monkey, and rat. A comparison of levels of radioactivity in blood or plasma, reached after intramuscular or intravenous administration, indicated that the drug was completely absorbed from the site of intramuscular injection within 10–15min in all three species. Within 1–5min after intramuscular or intravenous administration, the 21-phosphate ester was completely hydrolyzed to triamcinolone acetonide, which was present in the blood. The radioactivity was eliminated rapidly (t1/2 = 1–2 hr) from plasma (dogs, monkeys, and rats) and tissues (rats) after intramuscular or intravenous administration. In the three species, the major route of excretion was via the bile; however, the ratio of biliary to urinary excretion among the species varied considerably (from 1.5 to 15). In rats, excretion of radioactivity as expired carbon dioxide accounted for only 2–3% of the dose. 6β-Hydroxytriamcinolone acetonide was the major metabolite in urine of the three species. Hydrolytic cleavage of the acetonide group did not appear to be significant.