LABORATORY AND CLINICAL STUDIES ON FLOMOXEF IN NEONATES AND PREMATURE INFANTS

Flomoxef (FMOX), an oxacephem antibiotic of β-lactam antibiotic family, was administered to 16 infants including 6 neonates and 10 premature infants at a dose of 20 or 40mg/kg via intravenous injection, and plasma and urinary concentrations and the urinary recovery were determined. In addition, FMOX was administered via intravenous injection at daily doses averaging 85.5mg/kg divided into 2 to 4 times for durations averaging 9 days to 96 infants from 0-to 90-day old (mainly neonates and premature infants). In 44 of the 96 infants with bacterial infections, clinical and bacteriological efficacies were evaluated, and prophylactic effects of FMOX were determined in the remaining 52 infants. Adverse reaction and laboratory tests abnormalities were evaluated also. The obtained results are summarized as follows. 1. Upon administration of FMOX at 20 or 40mg/kg to neonates and premature infants via intravenous injection, plasma concentrations, half-lives and AUC were determined. In 3 neonates of 5, 7 and 16 days of ages administered with 20mg/kg of FMOX, peak plasma concentrations of 62.5 to 99.7μg/ml were achieved in 5 or 15 minutes after injection. Half-lives of FMOX in these neonates were 1.48 to 1.78 hours and AUC's were 112 to 161μg·hr/ml. The same dose (20mg/kg) of FMOX was administered to 3 premature infants of 5-16-and 19-day of ages and initial blood samples were obtained at 5 minutes after injection from the 5-day old subject and at 15 minutes after injection from the 16-and 19-day old subjects. Peak plasma concentrations of 63.6 to 79.9μg/ml were observed in the samples. Half-lives were 1.69 to 2.20 hours and AUC's were 174 to 201μg·hr/ml. When 3 neonates (one 17-day old and two 24-day old subjects) were administered with 40mg/kg of FMOX, peak plasma concentrations obtained at 5 minutes after injection were 99.7 to 122.0μg/ml. Half-lives were 1.28 to 1.92 hours and AUC's were 170 to 357μg·r/ml. In 6 premature infants (one 3-day old, one 5-day old and four between 16 and 24 days of ages) administered the same dose, the peak plasma concentrations achieved at 5 minutes after injection were as follows: 113.0μg/ml in the 3-day old, 108.0μg/ml in the 5-day old and between 112.0 and 148.0μg/ml in the other 4 cases, half-lives were 3.85, 2.86 and between 1.70 and 2.25 hours, respectively, and AUC's were 493, 407 and between 310 and 361μg·hr/ml, respectively, for the 3 groups of subjects. 2. Urinary concentrations and urinary recovery rates were also determined