乙氧苯柳胺在家兔体内的主要代谢产物

A STUDY ON THE MAJOR METABOLITE OF ETOFESALAMIDE IN RABBITS

采用高效液相色谱法对家兔口服乙氧苯柳胺（Ｎ－（４－乙氧苯基）－２－羟基苯甲酰胺）后在尿中的代谢物进行了分离与检测．用β－Ｄ－葡糖苷酸酶和该酶加专属性抑制剂葡糖二酸－１，４－内酯分别对尿样进行水解处理，发现该药的主要代谢物为β－Ｄ－葡糖醛酸结合物，其含量超过尿中代谢物总量的８０％．利用色谱保留值和紫外双波长吸收比对酶解后的主要生成物进行定性分析，证明该代谢物为乙氧苯柳胺葡糖醛酸结合物（Ｎ－（４－乙氧苯基）－苯甲酰胺－２－Ｏ－葡糖苷酸）．此外，在家兔给药后０～１２ｈ尿样中未检测出乙氧苯柳胺原形药物及其可能的代谢产物水杨酸．

After oral administration of etofesalamide (N-(4-ethoxyphenyl)-2-hydroxyl-benzamide)to rabbits, the metabolites in their urine were separated and detected with HPLC method.By treating the urine samples withβ-D-glucuronidase and with the same enzyme combined with its specific inhibitor saccharo-1,4-lactone,respectively,the major metabolite of etofesalamide was found to be aβ-D-glucuronide conjugate which amounted to more than 80%of urinary metabolites in concentration.The enzyme-hydrolyzed product of the major metabolite was characterized qualitatively by means of the chromatographic retention time and the ratio of its UV-absorbances at two wavelengthes.It was demonstrated that the metabolite is the glucuronide of etofesalamide (N-(4-ethoxyphenyl)-benzamide-2-O-β-D-glucuronide).In contrast,the parent drug and its potential metabolite salicylic acid were not detected in the urine after 0～12 h etofesalamde administration.