A new oligomeric derivative of thiadenol (TAD), in which the active principle is polyesterified with a bicarboxylic acid, has been studied as new retard-release prodrug (TAD-235). The compound has been acutely administered to rats and humans in order to assess, after oral administration, the dose-response serum levels of released TAD by means of a specific and sensitive enzyme immunoassay. The serum levels have been compared with those obtained by administration of TAD at equimolar dose. The results suggest an optimal bioavailability of the drug without high serum levels which, on the contrary, are constant over at least a 20-hour period. Finally, the prodrug TAD-235 was administered chronically to humans at a single daily dose of 500 mg/day, corresponding to 400 mg/day of active principle, which is five to six times lower than the dose of TAD currently used in the treatment of hyperlipidemic patients. A significant reduction of cholesterol and triglyceride levels has been observed after one month of treatment, suggesting the potential usefulness of TAD-235 as new hypolipidemic drug.
|Number of pages||7|
|Journal||Current Therapeutic Research|
|Publication status||Published - 1987|
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