Effect of Oral Pretreatment with Antibiotics on the Hydrolysis of Salicylic Acid-Tyrosine and Salicylic Acid-Methionine Prodrugs in Rabbit Intestinal Microorganisms

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We examined the hydrolysis mechanism of salicylic acid-tyrosine (salicyl-tyrosine) and salicylic acid-methionine conjugate (salicyl-methionine) in rabbits by exploring their behavior follwing intraduodenal and intracecal administration (72 and 36μmol/kg, respectively : salicylic acid equivalent). A large amount of salicyl-methionine was absorbed following intraduodenal administration of salicyl-methionine, without being metebolized to salicylic acid in the small intestinal mucosa. On the contrary, salicylic acid was detected in the blood follwing intraduodenal administration of salicyl-tyrosine, suggesting that salicyl-tyrosine was metabolized in the small intestinal mucosa.After oral pretreatment of rabbits with kanamycin sulfate (6×400mg) or tinidazole (6×160mg), the hydrolysis of salicyl-tyrosine and salicyl-methionine follwing intracecal administration was inhibited significantly, indicating that the intestinal microorganisms were responsible for the biotransformation of these prodrugs. Furthemore, in rabbits orally pretreated with both kanamycin sulfate and tinidazole, a significant inhibition of salicylic acid formation from salicyl-tyrosine and salicyl-methionine following intracecal administration was observed.
公益社団法人日本薬学会の論文
1992-09-25