Pharmacokinetics of cefoperazone in full-term and premature neonates

Abstract

The pharmacokinetics of cefoperazone were evaluated in 28 newborn infants who were being treated for sepsis. A dose of 50 mg/kg was administered intravenously on days 0 to 2 in all, with a second dose administered on days 5 to 7 in 14 infants. Cerebrospinal fluid penetration was also studied in seven neonates. The mean peak concentration of cefoperazone in the serum of premature infants < 33 weeks of gestational age, 159 (standard deviation, ± 22) μg/ml, was higher than concentrations in premature infants 33 to 36 weeks of age and full-term infants (110 ± 41 and 109 ± 29 μg/ml, respectively). The mean concentrations 24 h after dosage were similar in all three groups, 13 to 17 μg/ml. The mean serum half-lives were similar in the three subgroups and ranged from 7 to 9 h. After the dose at 5 to 7 days, mean blood levels in the subgroups at 0.5 h were 149, 112, and 112 μg/ml; 24-h levels ranged from 9 to 12 μg/ml. The mean serum half-lives ranged from 5 to 7 h. Cerebrospinal fluid levels in patients with meningitis ranged from 2.8 to 9.5 μg/ml and in patients without meningitis from 1 to 7 μg/ml. Peak blood levels were 15 to 1,000 times higher than the 90% minimal inhibitory concentration of common pathogens found in newborns. These observations support the potential efficacy of cefoperazone in treatment of infections, including meningitis, in newborn infants.