Cerebrospinal Fluid Pharmacokinetics of Cefpodoxime Proxetil in Piglets

Cefpodoxime is an oral third-generation cephalosporin used for the treatment of acute upper-respiratory tract infections caused by susceptible bacteria in children. Although not indicated for the treatment of bacterial meningitis, it is used to treat other infections produced by organisms associated with meningitis and may obscure the result of cerebrospinal fluid (CSF) cultures in children who develop meningitis while receiving oral antibiotics if sufficient concentrations are achieved in the CSF. This study evaluated the disposition of cefpodoxime and penetration into CSF in piglets. Fifteen Landacre-Camborough cross piglets (10-20 days old) received cefpodoxime proxetil oral suspension (10 mg/kg). Repeated plasma and CSF samples were collected over 24 hours for quantitation of cefpodoxime by HPLC. Pharmacokinetic analysis was performed on both plasma and CSF data. The plasma concentration versus time data for cefpodoxime were best characterized using a one-compartment model with first-order absorption. The mean (± SD) pharmacokinetic parameters for C max , t max , and AUC 0- ∞ were 23.3 ± 12.9 mg/L 3.9 ± 1.4 h, and 237 ± 129 mg/L.h, respectively. CSF/plasma ratios for AUC 0- ∞ demonstrated a mean cefpodoxime penetration of approximately 5%. CSF penetration of cefpodoxime was evident following a single oral dose of cefpodoxime proxetil suspension. Despite the small percentage of total cefpodoxime dose distributing into the CSF, the resultant concentrations approached or exceeded the MIC 90 for many bacterial pathogens considered susceptible to cefpodoxime. Accordingly, clinicians should use caution in the interpretation of CSF cultures in patients who develop clinical signs and symptoms consistent with meningitis and who have been previously treated with cefpodoxime.