Stability, Absorption and Excretion Studies with Hetacillin

Abstract

Hetacillin is a condensation product of ampicillin with acetone, in which the 6-amino group is part of an imidazoline ring. In aqueous solution hetacillin is rapidly hydrolysed to ampicillin and acetone. Half life times for the hydrolysis at pH between 3 and 8 were found to be about 30 minutes. The absorption and excretion characteristics of hetacillin were defined in comparison to ampicillin by crossover studies in normal subjects. The average peak serum concentration and the urinary excretion obtained with hetacillin was only half that with ampicillin. At 6 and 8 hours after dosing, however, the concentrations were slightly higher for hetacillin. The absorption pattern for hetacillin is similar to what the authors earlier observed with sustained release tablets of ampicillin. Low absorption rate of hetacillin as such and the rapid hydrolysis at the pH of the duodenal juice could explain this similarity.