A pharmacokinetic analysis of ampicillin in the cerebrospinal fluid of rabbits with staphylococcal meningitis.

Abstract

Pharmacokinetic differences between a bolus and a 60 minutes continuous intravenous administration of 100 mg/kg dose of ampicillin in the cerebrospinal fluid (CSF) were evaluated in the rabbits with experimental staphylococcal meningitis. The maximum concentrations in CSF were 19.3 micrograms/ml for bolus injection and 7.24 micrograms/ml for 60 minutes continuous infusion. Half-lives (T1/2) in CSF and CSF/serum ratios of T1/2 were 29.9 minutes and 1.3 minutes for bolus injection and 48.1 minutes and 1.9 minutes for 60 minutes continuous infusion, respectively. These findings indicate that extremely high concentrations of short duration in serum are required to elevate the concentrations in CSF and the maintenance of certain concentrations in serum are required to keep concentrations above the therapeutic concentrations in CSF. The mean penetration rate derived from the CSF/serum ratios of AUC were 11.1% for bolus injection and 5.5% for 60 minutes continuous infusion. Thus bolus injection is considered to be superior to 60 minutes continuous infusion pharmacokinetically. Bacterial meningitis is one of the diseases in which therapeutic concentrations of antibiotics are difficult to attain at the the site of infections. Therefore, when an intravenous ampicillin is going to be used in the treatment of bacterial meningitis, bolus injection is preferred to 60 minutes continuous infusion.