文章基本信息

标题：Proposal of Membrane Transport Mechanism of Protein-Unbound Ulifloxacin into Epithelial Lining Fluid Determined by Improved Microdialysis
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作者：Makoto Aoki ; Maki Iguchi ; Hiroyuki Hayashi 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2008
卷号：31
期号：9
页码：1773-1777
DOI：10.1248/bpb.31.1773
出版社：The Pharmaceutical Society of Japan
摘要：Microdialysis method (MD) is useful for sampling protein-unbound substances in vivo . Generally in the MD, a reference compound is used to correct differences in drug permeation clearance through a dialysis membrane in vivo and in vitro . No reference compound was, however, used for determination of a protein-unbound drug concentration in the epithelial lining fluid (ELF). In this study, we firstly examined the propriety of endogenous urea as a reference compound to determine the protein-unbound ulifloxacin concentrations in rat ELF by MD. Endogenous urea was used to correct differences in the permeation clearance in vivo and in vitro which reflect the differences in the extent of contact between a tip probe and ELF in vivo and in vitro . The results showed that our MD is applicable to determine the various concentrations of ulifloxacin and urea, and that we can use endogenous urea as a reference compound even if the extent of the contact between a tip of the probe and the ELF is small. In addition, use of urea concentrations does not affect drug distribution from plasma to ELF because we used endogenous urea. These results support usefulness of endogenous urea as a reference compound to determine protein-unbound drug concentration in ELF by MD. In addition, our results also suggest the existence of certain distribution mechanisms which cause the high penetration ulifloxacin into ELF. Our MD can help progress in pharmacokinetic-pharmacodynamic analysis of various antibiotics in the case where the concentrations in ELF are not equal to that in plasma.
关键词：epithelial lining fluid;microdialysis method;ulifloxacin;urea;rat