Nakamura J, Kido M, Nishida K, Sasaki H
School of Pharmaceutical Sciences, Nagasaki University, Japan.
Chem Pharm Bull (Tokyo). 1992 Sep;40(9):2572-5. doi: 10.1248/cpb.40.2572.
We examined the hydrolysis mechanism of salicylic acid-tyrosine (salicyl-tyrosine) and salicylic acid-methionine conjugate (salicyl-methionine) in rabbits by exploring their behavior following intraduodenal and intracecal administration (72 and 36 mumol/kg, respectively: salicylic acid equivalent). A large amount of salicyl-methionine was absorbed following intraduodenal administration of salicyl-methionine, without being metabolized to salicylic acid in the small intestinal mucosa. On the contrary, salicylic acid was detected in the blood following 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 x 400 mg) or tinidazole (6 x 160 mg), the hydrolysis of salicyl-tyrosine and salicyl-methionine following intracecal administration was inhibited significantly, indicating that the intestinal microorganisms were responsible for the biotransformation of these prodrugs. Furthermore, 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.
我们通过研究水杨酸 - 酪氨酸（水杨酰 - 酪氨酸）和水杨酸 - 蛋氨酸共轭物（水杨酰 - 蛋氨酸）在十二指肠内和盲肠内给药后的行为（分别为72和36 μmol/kg：水杨酸当量），研究了其在兔体内的水解机制。十二指肠内给予水杨酰 - 蛋氨酸后，大量水杨酰 - 蛋氨酸被吸收，未在小肠黏膜中代谢为水杨酸。相反，十二指肠内给予水杨酰 - 酪氨酸后，血液中检测到了水杨酸，这表明水杨酰 - 酪氨酸在小肠黏膜中发生了代谢。用硫酸卡那霉素（6×400 mg）或替硝唑（6×160 mg）对兔进行口服预处理后，盲肠内给药后水杨酰 - 酪氨酸和水杨酰 - 蛋氨酸的水解受到显著抑制，表明肠道微生物负责这些前药的生物转化。此外，在同时用硫酸卡那霉素和替硝唑口服预处理的兔中，观察到盲肠内给药后水杨酰 - 酪氨酸和水杨酰 - 蛋氨酸形成水杨酸受到显著抑制。
