PHARMACOKINETIC AND CLINICAL EVALUATION OF CEFTRIAXONE IN NEONATES AND PREMATURE INFANTS

Abstract

To 39 neonates and premature infants 1 to 28 days old with various bacterial infections or suspected bacterial infections and were nearing cure-stage via ceftriaxone (CTRX) therapy, CTRX 10mg/kg or 20mg/kg was intravenously administered by bolus injection, and the changes in serum concentrations and urinary recovery rates of the drug were examined. Because the number of cases included was small, a comparison study was conducted by classifying them into three groups; less than 4 days old, 4 to 7 days, and 8 days or older, rather than dividing them into groups of neonates and premature infants. Clinical evaluation was conducted in 10 male and 6 female cases 1 to 46 days old, whose diseases comprised 1 case each of purulent meningitis, septicemia, pyothorax, phlegmonous cellulitis, and staphylococcal scalded skin syndrome, plus 5 with bronchopneumonia and 6 with urinary tract infection.
1. Changes in serum concentrations and urinary recovery rates
(1) Intravenous bolus injection of 10mg/kg:
Serum concentrations in all three groups were the highest immediately after the drug administration, ranging from 32.3 to 35.9μg/ml, with no significant differences noted among the groups. The levels gradually declined thereafter in all groups; to 12.7 to 18.3μg/ml at 6 hours and 8.4 to 13.2μg/ml at 12 hours. Averaged blood half-lives of CTRX were 11.3, 8.8, and 17.3 hours. The urinary recovery rates in the first 6 hours in the 3 groups were 31.0, 27.9, and 26.0%, respectively.
(2) Intravenous bolus injection with 20mg/kg:
Serum concentrations were the highest immediately after the drug administration in all 3 groups, ranging from 56.5 to 73.1μg/ml. The levels gradually declined thereafter in all groups, but remained rather high at 17.9 to 21.1μg/ml at 6 hours and 13.2 to 16.8μg/ml at 12 hours. The older the patients were, the shorter the serum half-lives of CTRX were: 25.5 hours in the less than 4 day old group, 11.7 hours in the 4 to 7 day old group, and 10.5 hours in the 8 days or older group. The urinary recovery rates in the first 6 hours in the 3 groups were 25.5, 22.3, and 21.8%, respectively.
2. Clinical results
Clinical evaluation was made in 16 cases. CTRX at 11.9 to 60.0mg/kg/day, was administered once daily or in 2 divided doses, daily. In all cases, including those with presumed severe infections that included 1 case each of purulent meningitis, septicemia and pyothorax, the efficacy was good or excellent. Causative pathogens were bacteriologically identified in 15 cases, including 5 strains of Escherichia coli, 2 of Klebsiella pneumoniae, 5 of Staphylococcus aureus, 2 of Streptococcus pneumoniae, and 1 of Group B Streptococcus, but excluding case No.6 with bronchopneumonia. All of these bacteria were eradicated during the therapy.
3. Side effects
No subjective or objective side effects were observed in any case. Regarding laboratory abnormalities, GOT elevation was noted in only one case, and it was of no clinical significance.