Comparative disposition of sulindac and metabolites in five species
| Autor: | C.Gordan Van Arman, Daniel E. Duggan, Howard B. Hucker, Kay F. Hooke, R. M. Noll |
|---|---|
| Rok vydání: | 1978 |
| Předmět: |
Male
Sulfide Stereochemistry Metabolite Guinea Pigs Anti-Inflammatory Agents Biochemistry Redox Sulfone chemistry.chemical_compound Dogs Sulindac Biotransformation Species Specificity medicine Animals Bile Enterohepatic circulation Pharmacology chemistry.chemical_classification Sulfoxide Haplorhini Rats Kinetics chemistry Indenes Rabbits medicine.drug |
| Zdroj: | Biochemical pharmacology. 27(19) |
| ISSN: | 0006-2952 |
| Popis: | The disposition of the new anti-inflammatory agent,cis-5-fluoro-2-methyl-1-[ p -(methylenesulfinyl)-benzylidene]-indene-3-acetic acid [sulindac] and its sulfide and sulfone metabolites was studied in five laboratory species. In each, oxidative biotransformation of the parent sulfoxide (sulindac) to sulfone is irreversible, while reduction to sulfide is reversible. The areas under the plasma concentration curves [AUC] of each redox form vary within each species as a function of the form which is administered and, because of differences in the reversible biotransformations and in enterohepatic circulation, vary widely among species for any given redox form administered. Corresponding variations in anti-inflammatory responses, within species, is a monotonic function of the AUC of sulfide, but not of that for sulfoxide or sulfone. A similar correlation is apparent between intestinal toxicity, to the extent that it occurs, and cumulative biliary secretion of the sulfide. Thus, additional evidence is provided for the putative role of the sulfide metabolite as the biologically active form of sulindac. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|