Single-Dose Pharmacokinetics of Intravenous Sulbactam in Pediatric Patients

The pharmacokinetics of intravenously administered sulbactam were studied in 17 pediatric patients two to 14 years of age.Single doses of 12.5 or 25 mg/kg were infused over 3 min, and in previously healthy children, mean peak plasma concentrations 5 min after dosing were 71 and 163 ug/ml, respectively.Noncompartmental and compartmental calculations resulted in similar pharmacokinetic parameters.Linear pharmacokinetics were found in the concentration range studied.The mean terminal-phase half-life was 1.75hr, the mean total plasma clearance was 180 ml/min per 1.73 m-, and the mean apparent volume of distribution was 340 ml/kg.Approximately 70Ofo-80Ofo of an intravenous dose was excreted unchanged in the urine.In children with cystic fibrosis, both total plasma clearance and apparent volume of distribution were significantly increased.The data support the intravenous administration of 12.5-25 mg of sulbactam/kg every 6 to 8 hr for assessing the adequacy of this drug as an adjunct to 13-lactam therapy for various bacterial infections in children.An increasing number of gram-positive and gramnegative organisms that cause infections in children have become resistant to penicillin or cephalosporin compounds through the production of 13-lactamases, enzymes that destroy these antibiotics.One way of restoring the susceptibility of resistant strains of bacteria to these agents is by co-administering an inhibitor of 13-lactamases.Sulbactam is a potent and relatively stable 13-lactamase inhibitor that shows promise as an adjunct to 13-lactam therapy.The majority of the bacterial agents that cause respiratory tract infections (e.g., pneumonia, bronchitis, sinusitis, otitis), cellulitis, skeletal infections (e.g.arthritis, osteomyelitis), urinary tract infections, and meningitis in children are susceptible to sulbactam plus ampicillin.This group of pathogens includes the 13-lactamase-producing strains of Haemophi/us influenzae, Staphylococcus aureus, and Escherichia coli [1,2].In the present study we evaluated the pharmaco-Informed consent for these studies was obtained from the parents of the study patients.The guidelines of the local Institutional Committee on Human Investigations were followed in the conduct of this research.