Effect of BOF-4272 on the oxidation of allopurinol and pyrazinamide in vivo
| Autor: | Michio Suda, Toshikazu Hada, Yumiko Nasako, Keisai Hiroishi, Kazuya Higashino, Tetsuya Yamamoto, Sumio Takahashi, Yuji Moriwaki, Takashi Nakano |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
musculoskeletal diseases
Pharmacology congenital hereditary and neonatal diseases and abnormalities integumentary system biology Chemistry medicine.drug_class nutritional and metabolic diseases Allopurinol Pyrazinamide medicine.disease Biochemistry Gout chemistry.chemical_compound Xanthine dehydrogenase Enzyme inhibitor medicine biology.protein Xanthine oxidase Aldehyde oxidase Xanthine oxidase inhibitor medicine.drug |
| Zdroj: | Biochemical Pharmacology. 46:2277-2284 |
| ISSN: | 0006-2952 |
| DOI: | 10.1016/0006-2952(93)90618-7 |
| Popis: | Allopurinol or pyrazinamide was administered to rats treated with BOF-4272 (a potent xanthine oxidase inhibitor) to investigate to what degree xanthine dehydrogenase participates in the oxidation of these agents. BOF-4272 markedly decreased the plasma concentration and the urinary excretion of both oxypurinol and 5-hydroxypyrazinamide. It also decreased the sum of the urinary excretion of allopurinol and oxypurinol and that of pyrazinamide and its metabolites, although it did not affect the sum of the plasma concentrations of allopurinol and oxypurinol at 105 min after administration of allopurinol or the plasma concentration of pyrazinamide during the period after the administration of pyrazinamide. These results suggested that BOF-4272 almost completely inhibited the oxidation of allopurinol and pyrazinamide and had some effect on the excretion and/or the tissue incorporation of these two compounds. Since the in vitro study demonstrated that BOF-4272 did not inhibit the activity of aldehyde oxidase, which oxidized both allopurinol to oxypurinol and pyrazinamide to 5-hydroxypyrazinamide, the results suggested that xanthine dehydrogenase was the more important enzyme in converting allopurinol to oxypurinol and pyrazinamide to 5-hydroxypyrazinamide. |
| Databáze: | OpenAIRE |
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