Pharmacokinetic Study of the Association of Amoxicillin / Clavulanic Acid to Obese Adults (PHACO)

Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba

Status and phase

Completed

Phase 2

Phase 1

Conditions

Obesity

Treatments

Drug: amoxicillin and clavulanic acid

Study type

Interventional

Funder types

Other

Identifiers

NCT02571959

IMEA 046

Details and patient eligibility

About

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

Full 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.

Enrollment

36 patients

Sex

All

Ages

18 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Voluntary obese
Body mass index upper to 30 kg/m2
Age from 18 to 65 years
Signed free and lit consent
Possible participation according to the national file of the volunteers of the French Ministry of Health.
Volunteers affiliated to the Social Security

Exclusion criteria

Pregnancy
Evolutionary pregnancy or feeding
Allergy in ß-lactamines (nettle rash, oedema of Quincke)
Digestive intolerance with amoxicillin / clavulanic acid
Infection by the virus of the HIV ( positive Ac anti HIV)
Infection by the virus of the hepatitis B ( positive Ag Hbs)
Infection by the virus of the hepatitis C ( positive Ac anti VHC)
Hepatic cirrhosis at the Child-Pugh C stage(stadium)
Biological parameters:
Polynucléaires neutrophiles 750 / mm3
Haemoglobin 8g / dL
Patellets 60 000 / mm3
Creatinin clearance, according to MDRD, DFG 50 mL / min / 1,73m2
ASAT or ALAT > 3 times the superior limit of the normal (LSN)
Phosphatase alkaline > 3 LSN
Total Bilirubine > 3 LSN
Lipase > 3 LSN
Factor V < 50 %
Alcoholism chronicles (consumption superior to 30 g of alcohol a day, amount to 3 glasses of wine)
Significant anomaly of the electrocardiogram, in particular QTc > 450 msec
Subject susceptible not to respect the modalities of the study
Drug addiction intra venous
Any medical conditions which according to the judgment(sentence) of the investigator would may interfere with the moderate pharmacokinetic parameters
People placed under legal protection
Histories of bariatric surgery