Disposition and metabolism of a new steroidal anti-inflammatory agent, deflazacort, in cynomolgus monkeys

Abstract

1. The kinetics and metabolic fate of 2′-¹⁴C-deflazacort, a new steroidal anti-inflammatory agent, were studied in the cynomolgus monkey after both p.o. and i.v. administration (5mg/kg).

2. There is no unchanged deflazacort in the plasma or urine after either p.o. or i.v. treatment.

3. As judged from the plasma AUC and urinary elimination values, the oral availability of both total ¹⁴C and metabolites seems to be lowered because of a route-dependent first-pass.

4. Both radioactivity and the main metabolite (21-desacetyl deflazacort) are eliminated from the plasma with half-lives of 2-3.5 h. The i.v. administered ¹⁴C is eliminated mainly in the urine (52-55% of dose), but biliary excretion is also quantitatively important.

5. Six metabolites were isolated from urine and identified by physico-chemical analysis. Among them, desacetylated deflazacort and its 6β-hydroxy derivative were shown to be the major radioactive products in plasma and urine, respectively.

6. Minor metabolites were: 21-desacetyl, 6α-hydroxy deflazacort; 21-desacetyl, 5α, 1-eno, deflazacort; 21-desacetyl, 20β hudroxy deflazacort; and 21-desacetyl, 11-keto deflazacort.