Cerebrospinal fluid penetration after combined administration of cefotaxime and ampicillin to rabbits with staphylococcal meningitis.

The pharmacokinetics of cefotaxime and ampicillin in the cerebrospinal fluid (CSF) were studied by a HPLC method after administering each of the antibiotics singly or as a mixture to rabbits with experimental meningitis caused by Staphylococcus aureus. The half-lives of cefotaxime and desacetyl-cefotaxime in the serum and of ampicillin in the CSF were found to be significantly shorter in the mixture group than in the respective single administration groups. No other statistically significant differences were observed between the mixture and single administration groups with respect to the maximum concentrations (Cmax) of the antibiotics in the serum and the CSF, to the relative percentage of the Cmax of each antibiotic in the CSF to the Cmax in the serum, and to the relative percentage of the AUC of each antibiotic in the CSF to that in the serum. These results differ from earlier findings that the concentration of ampicillin in the CSF of rabbits was significantly lower in animals concomitantly dosed with latamoxef (moxalactam) and ampicillin than in a group dosed only with ampicillin.