Biotransformation of Halcinonide, a Systemic Topical Anti-inflammatory Corticosteroid, in Rat

Percutaneous absorption and metabolism of halcinonide (21-chloro-9α-fluoro 11β, 16α, 17α-trihydroxy-4-pregnen-3, 20-dione cyclic-16, 17-acetal), a synthetic topical antiinflammatory corticosteroid, were studied in rats with the use of 14C-labeled compounds. Greater parts of the dermally applied radioactivity were retained in the skin as the parent compound and 4.2 to 8.4 % of the dose was excreted into urine and feces within 5 days after application. When 14C-halcinonide was injected intravenously, the parent compound did not occur in urine and bile. However, various kinds of dechlorinated metabolites were found. Cell-free, skin and liver perfusion experiments were carried out to examine the site of metabolism of halcinonide. In contrast to the low metabolic activity seen in the skin, a very rapid detoxification rate in the liver tissue was observed. From these results, it is suggested that halcinonide is metabolized to various kinds of dechlorinated and reduced metabolites, and disappears from the body rapidly after absorption from the skin.