Hetacillin: A Chemical and Biological Comparison with Ampicillin

Hetacillin breaks down in aqueous solution to give ampicillin and acetone, both of which products have been identified chemically. The rate of breakdown is maximal between pH values 5 and 8, and is considerably slower under more acid conditions. The finding that hetacillin does not react with hydroxylamine at pH 7, taken in conjunction with other data presented, suggests that the antimicrobial activity of hetacillin may be low or even neglibible, and that it must be converted to ampicillin to show significant biological activity. In a small double cross-over trial, using 250 mg of hetacillin and ampicillin, no significant differences were observed either in peak blood levels or in the time for which useful levels were maintained. It is concluded that, while hetacillin is likely to be as effective an antibiotic as ampicillin, it is unlikely to be more effective, and thus that it does not represent a significant therapeutic advance.