Faropenem pharmacokinetics in AOM children following oral administration of faropenem medoxomil

Abstract number: P1253

Arguedas A., Dagan R., Rincon G., Wang E., Tosiello R., Echols R., Li J., Beaudry A., Gill S.

Objectives: Faropenem medoxomil (FM) is a novel oral prodrug antibiotic with in-vitro activity against common repiratory tract pathogens including activity against penicillin and MDR resistant S. pneumoniae. The objective of this dose-ranging study was to evaluate faropenem (FAR) pharmacokinetics in paediatric AOM.

Methods: In this phase II study, children with AOM (0.5–7yrs) received FM BID for 10 days. Blood was collected from 179 children at 0.5, 1, 2 and 4 hours post dose 1. In addition, a single blood sample was obtained at study Visit 2 (study Days 4–6) in 314 children over a range of time following dose administration on that day. Doses evaluated were 7.5, 15, 30 and 40 mg/kg. FAR plasma concentrations were determined using a validated LC-MS/MS assay with a lower limit of quantitation of 2.5 ng/mL. Individual subject FAR pharmacokinetic parameters on Day 1 were calculated using non-compartmental analysis.

Results: FAR plasma pharmacokinetics following oral administration of FM on Day 1 demonstrated increasing exposure with increasing dose. Median FAR Cmax values were 16.5, 26.0, 54.3, and 57.9 mg/L at doses of 7.5, 15, 30, and 40 mg/kg, respectively. Corresponding median AUC0–4 values were 20.4, 42.3, 93.0 and 112 mg*h/L, respectively. FAR plasma concentrations at Visit 2 were similar to those observed on Day 1.

Conclusions: FAR pharmacokinetic data in paediatric subjects confirmed dose-linearity of AUC, while Cmax values, although approximately linear, trended toward less than expected increases with increasing dose. Comparison of paediatric values with those observed in adults showed an increase of 1.8-fold in CL/F. As expected with a drug that is renally eliminated, a correlation was observed between increasing AUC with decreasing CrCl. No gender or age (0.5 to 7 years) related effects were observed with FAR pharmacokinetics. Similar FAR plasma concentrations were observed following repeat dosing indicating no substantial changes in FAR pharmacokinetics over time.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Location: Barcelona, Spain
Presentation type:
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