羧苄青霉素α-羧基酯的制备、水解及口服吸收

Preparation, hydrolysis, and oral absorption of alpha-carboxy esters of carbenicillin.

作者信息

Clayton J P, Cole M, Elson S W, Hardy K D, Mizen L W, Sutherland R

出版信息

J Med Chem. 1975 Feb;18(2):172-7. doi: 10.1021/jm00236a013.

Abstract

Twelve alpha-carboxy esters of carbenicillin, a parenteral broad spectrum semisynthetic penicillin, were synthesized and examined as potential oral carbenicillin derivatives. The rates at which the esters were hydrolyzed in vitro to carbenicillin by animal and human tissues were compared and the carbenicillin serum levels arising after oral administration of the esters were measured in squirrel monkeys and human volunteer subjects. The alpha-carboxyphenyl ester of carbenicillin [carfecillin (British Pharmacopoeia approved name), BRL 3475] WAS SELECTED FOR FURTHER STUDY AND IS PRESENTLY UNDERGOING CLInical trial.

摘要

合成了12种羧苄青霉素的α - 羧基酯，羧苄青霉素是一种注射用广谱半合成青霉素，并将其作为潜在的口服羧苄青霉素衍生物进行了研究。比较了这些酯在动物和人体组织中体外水解为羧苄青霉素的速率，并在松鼠猴和人类志愿者受试者中测量了口服这些酯后产生的羧苄青霉素血清水平。羧苄青霉素的α - 羧基苯基酯[卡非西林（英国药典批准名称），BRL 3475]被选作进一步研究，目前正在进行临床试验。