Pharmacokinetics of cefprozil in plasma and middle ear fluid: in children undergoing treatment for acute otitis media.
BACKGROUND
Despite the wide-scale use of cefprozil for acute otitis media (AOM), there are only limited data available regarding the pharmacokinetic profile of this agent in the pediatric population.


OBJECTIVE
To characterize the plasma and middle ear fluid (MEF) pharmacokinetic profile of cefprozil in pediatric patients with AOM.


METHODS
Pharmacokinetic sampling was obtained as part of a phase IV, multicenter, open-label study of children with AOM receiving cefprozil suspension 15 mg/kg twice daily. A single blood sample was obtained 4-6 days after the initiation of cefprozil therapy and a simultaneous MEF sample was obtained by tympanocentesis when clinically indicated. Cefprozil concentrations in both matrices were determined using a validated high-performance liquid chromatography methodology. A composite profile of cefprozil concentration data in each matrix was constructed and values for the pharmacokinetic parameters were obtained using conventional modeling techniques.


RESULTS
Plasma concentrations were obtained in 53 children aged 6-48 months. In this population the maximum concentration (C(max)) in plasma was 9.18 microg/mL, the time to C(max) (t(max)) was 1.5 hours, and the terminal elimination half-life (t((1/2))(beta)) was 0.98 hours. Simultaneous plasma and MEF concentration data were available in 22 children. In this subset the C(max) in plasma was 8.2 microg/mL, the t(max) was 1.9 hours, and the t((1/2))(beta) was 1.02 hours; the corresponding MEF C(max) was 2.4 microg/mL, the t(max) was 3.5 hours, and the t((1/2))(beta) was 1.23 hours. Cefprozil MEF penetration as assessed using the ratio of the area under the concentration-time curves from the two matrices was 28%. Moreover, concentrations in MEF approximated 1 microg/mL 6 hours' post-dose.


CONCLUSIONS
The plasma profile of cefprozil in the current analysis is consistent with previously reported values in children receiving the 15 mg/kg twice daily dose. MEF penetration and the duration of drug exposure at the site of infection support the clinical utility of this agent for organisms with minimum inhibitory concentrations (MIC) of < or =1 microg/mL. However, these results also predict higher clinical failure when using this dose of cefprozil against penicillin-non-susceptible Streptococcus pneumoniae or Haemophilus influenzae because of typically higher MIC values for these organisms.
Nicolau
David P
DP
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut 06102-5037, USA. dnicola@harthosp.org
Sutherland
Christina A
CA
Arguedas
Adriano
A
Dagan
Ron
R
Pichichero
Micheal E
ME
D000208:Acute Disease; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019540:Area Under Curve; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004432:Ear, Middle / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007223:Infant; D010033:Otitis Media / Q000188:drug therapy*; D000097670:Cefprozil
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097670:Cefprozil