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The pharmacokinetic and chemotherapeutic properties of the new penem antibiotic HRE 664 (Fig. 1) were evaluated in experimental animals. High and sustained blood and serum levels were achieved following parenteral injection in mice, rats, dogs and monkeys. Half-lives ranged from 27 to 40 minutes in the various species tested. The antibiotic was well distributed in the rodents and penetrated well into tissues and body fluids. At 30 minutes after subcutaneous administration to mice (50 mg/kg), concentrations of between 12.4 and 35.9 micrograms/g were measured in the lungs, liver, heart and kidneys, that is 33 approximately 95% of the corresponding level in murine blood (37.7 micrograms/ml). In experimentally induced infections in mice, HRE 664 displayed good chemotherapeutic activity particularly against septicemias caused by methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains and on abscess formation induced by Bacteroides fragilis. Most of the cephalosporins and other beta-lactam antibiotics exhibited low efficacy against these strains of bacteria.

HRE 664, a new parenteral penem. II. Evaluation of the pharmacokinetic behavior and the chemotherapeutic activity in animals.