Population Pharmacokinetic Analysis of Daptomycin in Patients With Osteoarticular Infections
Daptomycin is validated as a treatment of bone and joint infections by the Infectious Disease Society of America. However, most of studies did not investigate daptomycin pharmacokinetics in this indication while it is known that efficacy and toxicity concentration studies show a close therapeutic margin.
Evaluation of P-Glycoprotein (P-gp), a transmembrane transport protein, has demonstrated its influence on the concentration and intracellular activity of daptomycin. Recent work has linked the genetic polymorphism of P-gp to the pharmacokinetics of daptomycin, which may explain inter-individual variability but requires further explorations. Previous studies demonstrated existence of interindividual variabilities as sex, renal function and p-glycoprotein polymorphism couple with an intraindividual variabilities unexplained yet.
A population approach will be used to determinate the pharmacokinetics factors, their intra and interindividual variabilities, the parameters associated to those variabilities (as the p glycoprotein).
The investigator's goal is to evaluate different posology and to try to increase daptomycin efficacy and security in bone and joint infection.
研究概览
研究类型
注册 (实际的)
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
Inclusion Criteria:
Patients
- having had a bone or joint infection, with or without implant,
- having an antibiotherapy with daptomycin between December 2012 and December 2016 at the Croix-Rousse hospital
- are at least 18 years old
Exclusion Criteria:
- None
学习计划
研究是如何设计的？
设计细节
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
Peak plasma concentration (Cmax)
大体时间：Month 6
|
Month 6
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Area under the concentration-time curve
大体时间：up to 6 months
|
up to 6 months
|
|
|
typical daptomycin clearance and volume of distribution in the population
大体时间：Month 6
|
Month 6
|
|
|
Mean daptomycine plasma clearance
大体时间：Month 6
|
(unit, liters per hour)
|
Month 6
|
|
Mean daptomycine volume of distribution
大体时间：Month 6
|
(unit, liters)
|
Month 6
|
|
Inter-individual coefficient of variation of daptomycin clearance
大体时间：Month 6
|
(unit, %)
|
Month 6
|
|
Inter-individual coefficient of variation of daptomycin volume of distribution
大体时间：Month 6
|
(unit, %)
|
Month 6
|
|
Intra-individual coefficient of variation of daptomycin clearance
大体时间：Month 6
|
(unit, %)
|
Month 6
|
|
Intra-individual coefficient of variation of daptomycin volume of distribution
大体时间：Month 6
|
(unit, %)
|
Month 6
|
|
influence of demographic and biological covariates on pharmacokinetics (e.g. : renal function, gender)
大体时间：Month 6
|
the influence of demographic and biological covariates on pharmacokinetics will be assessed statistically by using the Akaike Information Criterion (AIC, no unit).
AIC = -2xLL + 2P, where LL is the log-likelihood computed by the population algorithm and P is the number of parameters in the model.
A covariate will be considered as significant if it is associated with a decrease in the AIC value compared with the base model without covariate.
|
Month 6
|
|
influence of p-glycoprotein pharmacogenetics on daptomycin pharmacokinetics
大体时间：Month 6
|
the influence of P-glycoprotein pharmacogenetics on pharmacokinetics will be assessed statistically by using the Akaike Information Criterion (AIC, no unit).
AIC = -2xLL + 2P, where LL is the log-likelihood computed by the population algorithm and P is the number of parameters in the model.
The P-glycoprotein genotype will be considered as significant if it is associated with a decrease in the AIC value compared with the base model without covariate.
|
Month 6
|
合作者和调查者
调查人员
- 首席研究员：Tristan Ferry、Hospices Civils de Lyon - Hôpital de la Croix Rousse
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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