抗生素的血药浓度PKPD approach for antibioticstissue or blood drug level to predict antibiotic efficacy.pptVIP

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2019-05-22 发布于江西
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抗生素的血药浓度PKPD approach for antibioticstissue or blood drug level to predict antibiotic efficacy.ppt

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PK/PD approach for antibiotics: tissue or blood drug level to predict antibiotic efficacy PL Toutain National Veterinary school; Toulouse First (scientific) consensus:The goal of PK/PD indices The goal of PK/PD indices is to predict, in vivo, clinical outcomes: Cure prevention of resistance Plasma free concentration is the relevant concentration for the establishment of a PKPD indice Second (marketing) consensus It is more easy to promote a macrolide showing its high lung concentrations than its low plasma concentrations PK/PD approach for antibiotics: tissue or blood drug level to predict antibiotic efficacy Objectives of the presentation: The three PK/PD indices Where are located the bugs ? Extracellular vs. intracellular Where is the biophase? Interstitial space fluid vs. intracellular cytosol vs. intracellular organelles How to assess the biophase antibiotic concentration Total tissular concentration vs. ISF concentration. The issue of lung penetration Epithelial lining fluid (ELF):? he hypothesis of targeted delivery of the active drug at the infection site by phagocytes Plasma as the best surrogate of biophase concentration for PK/PD interpretation The three PK/PD indices By essence the three PK/PD indices are hybrid parameters PK PD AUC/MIC Time MIC Cmax / MIC PK/PD indices are hybrid parameters For all indices: the PD input is the MIC The PK input is associated to plasma: why? And why not: the actual concentration at the site of action (biophase) the concentration of the tissue (organs) in which the infection develops What is an ideal concentration for a PK/PD indice A relevant concentration to serve as an input in a PK/PD model should be selective of the biophase i.e. of the fluid that bath the extracellular space namely the interstitial fluid (ISF). Q1: Where are located the pathogens and where is the biophase Where are located the pathogens ISF Most pathogens of clinical interest S. Pneumoniae, E. Coli,Klebsiella Mannhemia ; Pasteure