Recovery rates of combination antibiotic therapy using in vitro microdialysis simulating in vivo conditions  

作　　者：Jayesh A.Dhanani Suzanne L.Parker Jeffrey Lipman Steven C.Wallis Jeremy Cohen John Fraser Adrian Barnett Michelle Chew Jason A.Roberts 

机构地区：[1]Burns, Trauma and Critical Care Research Centre, The University of Queensland, UQ Centre for Clinical Research [2]Department of Intensive Care Medicine, Royal Brisbane & Women's Hospital [3]Faculty of Health, Queensland University of Technology [4]Critical Care Research Group, The University of Queensland [5]Institute of Health and Biomedical Innovation & School of Public Health and Social Work, Queensland University of Technology [6]Department of Anaesthesiology and Intensive Care, and Department of Medical and Health Sciences, Link?ping University [7]School of Pharmacy, The University of Queensland [8]Department of Pharmacy, Royal Brisbane & Women's Hospital

出　　处：《Journal of Pharmaceutical Analysis》2018年第6期407-412,共6页药物分析学报（英文版）

基　　金：funded by the TPCH foundation grant (MS201140);the RBWH foundation grant 2012;funding from the Australian National Health and Medical Research Council for a Centre of Research Excellence (APP1099452);funded in part by a Practitioner Fellowship (APP1117065) from the National Health and Medical Research Council of Australia

摘　　要：Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20μg/mL and flow rate of 1.0μL/min had the best recovery. A concentration of 5.0μg/mL and flow rate of 1.0μL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20μg/mL and flow rate of 1.0μL/min had the best recovery. A concentration of 5.0μg/mL and flow rate of 1.0μL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.

关 键 词：MICRODIALYSIS COMBINATION antibiotic therapy Relative recovery rate PHARMACOKINETICS ANTI-INFECTIVES Protein BINDING 

分 类 号：R[医药卫生]