PHTHALIDYL D-α-AMINOBENZYLPENICILLINATE HYDROCHLORIDE (PC-183), A NEW ORALLY ACTIVE AMPICILLIN ESTER

I. ABSORPTION, EXCRETION AND METABOLISM OF PC-183 AND AMPICILLIN

Abstract

Absorption, excretion and metabolism of a new ampicillin derivative, phthalidyl D-α-aminobenzylpenicillinate hydrochloride (PC-183), were studied. In comparison with
ampicillin, PC-183 showed the following characteristics.1. Upon oral administration in rats and humans, PC-183 was hydrolyzed and produced much higher plasma le urinary excretion of ampicillin was greater for PC-183 in both species. Concentration in tissues and bile of the rat was also higher for PC-183 than for ampicillin. These facts demonstrate superior intestinal absorption for PC-183 as compared with ampicillin.
2. The compound was easily hydrolyzed in the presence of rat tissue extracts, such as liver, kidney or small intestine. This hydrolysis was also catalyzed by blood plasma, the activity of which was highest in rats and mice, followed by humans anddogs in that order. The hydrolysis was so rapid that any attempt to detect intact PC-183 in blood, urine and tissues after oral administration to rats and humans was unsuccessful.
3. The hydrolysis products were ampicillin and phthalaldehydic acid. The latter was further metabolized to α-hydroxy-o-toluic acid and excreted into urine exclusively in this form. The metabolic pathway was the same for mice, rats, dogs and humans.