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

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.