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.
調査の概要
研究の種類
入学 (実際)
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
Peak plasma concentration (Cmax)
時間枠：Month 6
|
Month 6
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Area under the concentration-time curve
時間枠：up to 6 months
|
up to 6 months
|
|
|
typical daptomycin clearance and volume of distribution in the population
時間枠：Month 6
|
Month 6
|
|
|
Mean daptomycine plasma clearance
時間枠：Month 6
|
(unit, liters per hour)
|
Month 6
|
|
Mean daptomycine volume of distribution
時間枠：Month 6
|
(unit, liters)
|
Month 6
|
|
Inter-individual coefficient of variation of daptomycin clearance
時間枠：Month 6
|
(unit, %)
|
Month 6
|
|
Inter-individual coefficient of variation of daptomycin volume of distribution
時間枠：Month 6
|
(unit, %)
|
Month 6
|
|
Intra-individual coefficient of variation of daptomycin clearance
時間枠：Month 6
|
(unit, %)
|
Month 6
|
|
Intra-individual coefficient of variation of daptomycin volume of distribution
時間枠：Month 6
|
(unit, %)
|
Month 6
|
|
influence of demographic and biological covariates on pharmacokinetics (e.g. : renal function, gender)
時間枠：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
時間枠：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
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Tristan Ferry、Hospices Civils de Lyon - Hôpital de la Croix Rousse
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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