Methodological issues in microdialysis sampling for pharmacokinetic studies

Microdialysis is an in vivo technique that permits monitoring of local conc entrations of drugs and metabolites at specific sites in the body. Microdia lysis has several characteristics, which makes it an attractive tool for ph armacokinetic research. About a decade ago the microdialysis technique ente red the field of pharmacokinetic research, in the brain, and later also in peripheral tissues and blood. Within this period much has been learned on t he proper use of this technique. Today, it has outgrown its child diseases and its potentials and limitations have become more or less well defined. A s microdialysis is a delicate technique for which experimental factors appe ar to be critical with respect to the validity of the experimental outcomes , several factors should be considered. These include the probe; the perfus ion solution; post-surgery interval in relation to surgical trauma, tissue integrity and repeated experiments; the analysis of microdialysate samples; and the quantification of microdialysate data. Provided that experimental conditions are optimized to give valid and quantitative results, microdialy sis can provide numerous data points from a relatively small number of indi vidual animals to determine detailed pharmacokinetic information. An exampl e of one of the added values of this technique compared with other in vivo pharmacokinetic techniques, is that microdialysis reflects free concentrati ons in tissues and plasma. This gives the opportunity to assess information on drug transport equilibration across membranes such as the blood-brain b arrier, which already has provided new insights. With the progress of analy tical methodology, especially with respect to low volume/low concentration measurements and simultaneous measurement of multiple compounds, the applic ations and importance of the microdialysis technique in pharmacokinetic res earch will continue to increase. (C) 2000 Elsevier Science BN. All rights r eserved.