Pharmacokinetic Study of the Amoxicillin / Clavulanic Acid Association to Optimize Dosage Among Obese Adults (PHACO)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- Systematic plasmatic clearance (Cl)
研究概览
简要总结
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
详细描述
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 ).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
amoxicillin and clavulanic acid
All volunteers receive a dose of amoxicillin and clavulanic acid
干预措施: amoxicillin and clavulanic acid (Drug)
结局指标
主要结局
Systematic plasmatic clearance (Cl)
时间窗: 1 day
次要结局
- Volume of distribution (Vd)(1 day)
- Bioavailability after oral administration (F)(1 day)
- Constant of speed of absorption (Ka)(1 day)
- Area under the curve time - concentration (AUC 0-oo)(1 day)
- Half-life time (T1/2)(1 day)