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Published on: January 2, 2017

Variations in amoxicillin pharmacokinetic/pharmacodynamic parameters may explain treatment failures in acute otitis

Michael E Pichichero1, Michael D Reed

  • 1Rochester General Research Institute, Legacy Pediatric Group, Rochester, New York, USA. Michael.Pichichero@rochestergeneral.org

Paediatric Drugs
|July 2, 2009
PubMed

Insights

Amoxicillin therapy for acute otitis media (AOM) can fail due to high bacterial resistance or variable drug levels. Patient-to-patient differences in amoxicillin serum and middle ear fluid concentrations may explain treatment failures.

Area of Science:

  • Pediatric Infectious Diseases
  • Pharmacokinetics and Pharmacodynamics (PK/PD)
  • Microbiology

Background:

  • Pharmacokinetic/pharmacodynamic (PK/PD) models predict amoxicillin success in acute otitis media (AOM).
  • However, clinical outcomes sometimes deviate from these predictions, suggesting unaddressed factors.
  • Exceptions to expected amoxicillin efficacy in AOM are noted, particularly with resistant pathogens.

Purpose of the Study:

  • To investigate biological variations in amoxicillin PK/PD parameters for pediatric AOM treatment.
  • To determine if PK/PD variability explains imperfect prediction of amoxicillin treatment outcomes in AOM.
  • To analyze amoxicillin absorption, serum, and middle ear fluid (MEF) concentrations in children.

Main Methods:

  • Literature search of MEDLINE (1966-2006) and EMBASE (1974-2006).
  • Inclusion of studies evaluating ampicillin or amoxicillin intestinal absorption, serum, and MEF concentrations.
  • Analysis of PK/PD data to identify sources of variability.

Main Results:

  • Amoxicillin bioavailability is influenced by passive diffusion and a saturable 'pump' mechanism.
  • Significant inter-patient variability (5- to 30-fold) in serum and (up to 20-fold) in MEF amoxicillin concentrations observed.
  • 15-35% of children showed no detectable amoxicillin in MEF.

Conclusions:

  • Variability in amoxicillin PK/PD parameters significantly impacts drug concentrations in serum and MEF.
  • This pharmacokinetic variability likely contributes to treatment failures in pediatric AOM.
  • Current PK/PD models may underestimate the impact of inter-individual variability on amoxicillin efficacy in AOM.

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