Population Pharmacokinetic Analysis of Daptomycin in Patients With Osteoarticular Infections
试验速览
- 阶段
- 不适用
- 入组人数
- 189
- 主要终点
- Peak plasma concentration (Cmax)
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- 未提供
结局指标
主要结局
Peak plasma concentration (Cmax)
时间窗: Month 6
次要结局
- Mean daptomycine volume of distribution(Month 6)
- Intra-individual coefficient of variation of daptomycin clearance(Month 6)
- Inter-individual coefficient of variation of daptomycin clearance(Month 6)
- influence of demographic and biological covariates on pharmacokinetics (e.g. : renal function, gender)(Month 6)
- Area under the concentration-time curve(up to 6 months)
- typical daptomycin clearance and volume of distribution in the population(Month 6)
- Mean daptomycine plasma clearance(Month 6)
- Inter-individual coefficient of variation of daptomycin volume of distribution(Month 6)
- Intra-individual coefficient of variation of daptomycin volume of distribution(Month 6)
- influence of p-glycoprotein pharmacogenetics on daptomycin pharmacokinetics(Month 6)