Barbara Weissberger

QUATERNARY HETEROCYCLYLAMINO β-LACTAMS

Two newly described quaternary heterocyclylamino beta-lactams, L-642,946 and L-652,813, were shown to exhibit potent activity against a broad spectrum of aerobic and anaerobic bacteria in vitro. The activity of these agents in vitro translated well to chemotherapeutic activity in experimental bacteremias in mice. Substitution of the thiadiazine moiety of L-642,946 with a triazine moiety effected a marked change in the pharmacokinetics of the new derivative, L-652,813. In mice given a 20 mg/kg subcutaneous dose, the peak serum concentration and the half-life of L-652,813 were about three times greater than those of L-642,946 and the area under the serum concentration/time curve was increased by about 5-fold. The pharmacokinetics of L-652,813 in mice and in rhesus monkeys more closely resembled those of ceftriaxone which carries the same triazine moiety on the C-3 side chain.