Cardenolide analogues. VI. The metabolism of the prodrug diacetylcymarol in the rat.

1. Diacetylcymarol is an acetylated glycoside which is better absorbed than the parent glycoside, cymarol. 2. Diacetyl[19-3H]cymarol was rapidly metabolized and excreted by the rat following intraperitoneal administration. 3. The drug was metabolized extensively to polar compounds with the principal pathway involving loss of the C-19 acetyl group and probable demethylation of the sugar. 4. The bulk of the radioactive material was excreted in the bile and there was little reabsorption. 5. The results show that acetylation was successful in converting the poorly absorbed glycoside, cymarol, into a derivative that was rapidly absorbed from the peritoneal cavity. 6. Following or during absorption, the biologically inactive diacetylcymarol was converted to polar derivatives with potential therapeutic activity. However, subsequent elimination was so rapid that little therapeutic benefit could be expected.