Studies on the Development of Prodrugs Utilizing Microbial Activity in the Intestine.
| Project/Area Number |
01571215
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Nagasaki University |
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Principal Investigator |
NAKAMURA Junzo Nagasaki University. School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30115901)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | gut flora / prodrug / metabolism / intestinal absorption / salicylic acid / salicyluric acid / rabbit / dog |
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| Research Abstract |
The significance of the intestinal microorganisms to pharmacokinetics and biopharmacy has been emphasized with respect to their ability to metabolize drugs and foreign compounds. In the previous reports, we examined the blood concentration of salicyluric acid and salicylic acid following the intravenous, oral, intracecal and rectal administration of salicyluric acid in rabbits, rats and dogs. In these species, salicyluric acid is metabolized to salicylic acid by intestinal microorganisms. Following rectal administration of salicyluric acid, prolonged blood concentration of salicylic acid was observed. However, species difference in the metabolic fate of salicyluric acid following oral and intravenous administration was recognized. Furthermore, the effect of fasting and pretreatment with antibiotics on the hydrolysis of salicyluric acid was investigated in rabbits. Significant effect of fasting on the blood concentration of salicylic acid after oral administration of salicyluric acid was observed. However, no effect was found in its blood concentration following rectal administration. It seems that the slow rate of stomach emptying due to coprophagy during fasting is the principal reason for the change of blood concentration of salicylic acid after its oral administration. In rabbits pretreated with latamoxef sodium intravenously, slight effect was found on the blood concentration of salicylic acid following oral and rectal administration of salicyluric acid. On the other hand, significant effect of oral pretreatment with cephalexin on the blood concentration of salicylic acid following oral administration of salicyluric acid was observed.
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Report
(3 results)
Research Products
(9 results)
