Cerebrospinal fluid pharmacokinetics of cefpodoxime proxetil in piglets

Cefpodoxime Its an oral third-generation cephalosporin used for the treatme nt of acute upper-respiratory tract infections caused by susceptible bacter ia in children. Although not indicated for the treatment of bacterial menin gitis, if is used to treat other infections produced by organisms associate d with meningitis and may obscure the result of cerebrospinal fluid (CSF) c ultures in children who develop meningitis while receiving oral antibiotics if sufficient concentrations are achieved in the CSR This study evaluated the disposition of cefpodoxime and penetration into CSF in piglets. Fifteen Landacre-Camborough cross piglets (10-20 days old) received cefpodoxime pr oxetil oral suspension (10 mg/kg). Repeated plasma and CSF samples were col lected over 24 hours for quantitation of cefpodoxime by HPLC. Pharmacokinet ic analysis was performed on both plasma and CSF data. The plasma concentra tion versus time data far cefpodoxime were best characterized using a one-c ompartment model with first-order absorption. The mean (+/- SD) pharmacokin etic parameters for C-max, t(max), and AUC(0-infinity) were 23.3 +/- 12.9 m g/L, 3.9 +/- 1.4 h, and 237 +/- 129 mg/L . h, respectively CSF/plasma ratio s for AUC(0-infinity) demonstrated a mean cefpodoxime penetration of approx imately 5%. CSF penetration of cefpodoxime was evident following a single o ral dose of cefpodoxime proxetil suspension. Despite the small percentage o f total cefpodoxime dose distributing into the CSF, the resultant concentra tions approached or exceeded the MIC90 for many bacterial pathogens conside red susceptible to cefpodoxime. Accordingly, clinicians should use caution in the interpretation of CSF cultures in patients who develop clinical sign s and symptoms consistent with meningitis and who have been previously trea ted with cefpodoxime.