Pharmacokinetic and clinical evaluation of cefozopran in premature and newborn patients

Cefozopran (SCE-2787, CZOP), which is already on the market with a variety of approved indications in infectious diseases for adult patients, was administered to premature and newborn patients to evaluate the pharmacokinetics and the clinical efficacy. 1. Pharmacokinetics CZOP was intravenously administered at doses of 10.0 mg/kg, 21.4 mg/kg and 40.0 mg/kg to premature and newborn patients, and the blood concentrations and urinary excretion rate were examined. The blood CZOP concentrations were 31.7 and 65.5 micrograms/ml at 30 minutes after administration of 10.0 mg/kg and 40.0 mg/kg, respectively. The elimination half life was 1.78 hours and 2.31 hours, and the urinary recovery was 110.7% and 53.7% within 6 hours after administration, respectively. In the patient given 21.4 mg/kg, the blood CZOP concentration was 36.4 mg/kg at 1 an hour after administration and the elimination half life was 3.97 hours. The urinary recovery was 29.6% within 5 hours after administration. 2. Clinical results The clinical efficacy was evaluated in 19 patients and judged "good" or better in 13 of them with the efficacy rate or 68.4%. The bacteriological response was evaluated in 10 patients from whom Gram-positive cocci of S. aureus (6 strains), S. pneumoniae (1 strain) and E. faecalis (1 strain) and Gram-negative bacilli of H. influenzae (2 strains) and E. coli (2 strains) were isolated as possible causative organisms. With exception of 1 strain each of S aureus and H influenzae, which were not tested after the treatment with CZOP, all of these strains were found to be eradicated. 3. Adverse drug reactions (ADRs) of signs and symptoms and abnormal alterations of laboratory test values. Safety evaluation was made in 24 patients. ADRs of signs and symptoms were recognized in none of them. As abnormal alterations of laboratory test values, increased eosinophils in 3 patients, elevated GOT in one and elevated GPT in one were recognized. These results indicate that CZOP is a drug useful for treatment of infections in premature and newborn patients.