Development of an intravenous microdialysis method for pharmacokinetic investigations in humans
- 作者：Jan-Peer Elshoff and Stephanie Lä ; er
- 关键词：Methods ; In vitro microdialysis cell ; Intravenous microdialysis ; Retrodialysis by calibrator ; Pharmacokinetics ; Children ; Sotalol
- 刊名：Journal of Pharmacological and Toxicological Methods
- 出版年：2005
- 期刊代码：28_10568719
- 类别：pha
- 出版时间：2005
- 卷：52
- 期：2
- 页码：251-259
- 文件大小：199 K
摘要
Introduction: Limited blood volume is a major problem in pharmacokinetic investigations in specific populations, e.g. children. Intravenous microdialysis might help to obtain improved data sets as it is already successfully done in small animals. Since quantification of drugs is crucial in microdialysis, we developed an in vitro method to produce a workable intravenous microdialysis for human use. Methods: A specifically designed microdialysis cell consisting of glass was heated to 37 °C. The cell was filled with Ringer's solution, plasma or whole blood. A microdialysis probe was inserted into the cell and perfused with Ringer's solution with addition of 4%dextran. The β-receptor blocker sotalol served as a test drug. The stepwise in vitro evaluation process addressed issues of loss of dialysate, calibration by retrodialysis and relative recovery. These conditions were then applied in an in vivo pilot study to one single healthy volunteer after written informed consent. Results: To address loss of perfusion fluid 4%of dextran was added and high and constant amounts of dialysate were achieved. To account for changes in the relative recovery a continuous use of retrodialysis by the calibrator atenolol was introduced. The recovery of atenolol was comparable to sotalol. The pharmacokinetic analysis revealed that sotalol concentrations from microdialysates were not different from conventional plasma samples (100±11%, n