Pharmacokinetic Study of the Association of Amoxicillin / Clavulanic Acid to Obese Adults
Condition: Obesity
MeSH terms: Obesity
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Description of the pharmacokinetic parameters of the amoxicillin / clavulanic acid to healthy
      voluntary obese after oral and intra venous administration Determination of the
      pharmacokinetic parameters of amoxicillin / clavulanic acid obtained from plasmatic
      concentrations of intravenous injection (IV) and oral administrations. The criterion of
      evaluation allowing to answer our main objective corresponds to the parameters estimated by
      the pharmacokinetic model of the concentrations obtained from the data IV and by the
      pharmacokinetic model of the concentrations obtained from the oral data. The following
      pharmacokinetic parameters will be considered at every obese volunteer's for both molecules
      (amoxicillin and clavulanic acid) from the concentrations by pharmacokinetic analysis of
      population.

      The main evaluation criteria are PK parameters of amoxicillin / clavulanic:

        -  Cl, systematic plasmatic clearance

        -  Vd, volume of distribution

        -  ASC 0-oo, area under the curve time - concentration

        -  T1/2, half-life time

        -  F, bioavailability after oral administration

        -  Ka, constant of speed of absorption
    

Detailed description: 
      Main objective Description of the pharmacokinetic parameters of the amoxicillin / clavulanic
      acid to healthy voluntary obese after oral and intra venous administration

      Secondary objectives

        -  Define dosage plans optimized with the antibiotic treatment to the obese subject

        -  Ensure an adequacy of the treatment with the related infection

        -  Formulate recommendations of dosage adaptations for a better individualization of
           treatments, by estimating several plans of doses by simulation to reach various PK/PD
           goals according to different theoretical MIC

      Methodology

      The pharmacokinetic analysis will be realized by approach of population allowing the
      estimation of the average parameters of amoxicillin and clavulanic acid as well as the
      interpersonal variability after an administration IV and an oral administration. Parameters's
      population and their variability will be estimated with the SAEM algorithm implemented in the
      software Monolix ( www.lixoft.eu ).

      For the main objective, PK parameters PK of amoxicillin and clavulanic acid will be
      determined to day 1 and day 2. They will be described by means of indicators of position
      (average and median) and of dispersal (standard deviations, quartiles).

      For secondary objectives, the profiles concentration/time of 1000 obese subjects will be
      determined by Monte Carlo method from PK parameters estimated at the balance by the model.
      For every feigned profile, the time during which the plasmatic concentration of amoxicillin
      and clavulanic acid is superior to a panel of theoretical MIC will be calculated by means of
      curves concentration - time determined for each of the subjects.
    

Intervention name(s): amoxicillin and clavulanic acid; amoxicillin and clavulanic acid
Intervention type(s): Drug; Drug
Intervention description(s): Day 1 : a dose of amoxicillin and clavulanic acid 1g / 200mg will be intravenously administered; Day 2 : a dose of amoxicillin and clavulanic acid 1g / 125mg will be administered by oral route
Other intervention name(s): AMOXICILLINE / acide clavulonique SANDOZ; AMOXICILLINE / acide clavulonique SANDOZ
Intervention MeSH terms: Amoxicillin; Clavulanic Acids; Clavulanic Acid
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Obesity; Pharmacology; Amoxicillin-Potassium Clavulanate Combination