Microdialysis Techniques In Pharmacokinetic and Biomarker Studies Past, Present and Future Directions A Review

Abstract

Microdialysis (MD) techniques were first applied in the early 1960s. The fields of their application comprised probe implantation into the central nervous system (CNS) at the beginning, and then expanded to almost every organ summarized in this article. After its early experimental applications MD became an important tool in the human pharmacokinetic/pharmacodynamic (PK/PD) studies as well. This monitoring technique is capable for investigation of local unbound concentrations of both endogenous and exogenous compounds in the interstitial fluid. The review shows examples for the role of MD in pharmacodynamic studies and for its use in tissue distribution and drug-transporter interaction studies. Determination of test substances in the dialysate samples needs sensitive bioanalytical methods. The main analytical techniques coupled with MD are summarized under the subtitle "Target molecules". New trend in the application of MD is the determination of large molecular entities in the extracellular fluid of target tissues. This approach greatly helps in the discovery of new pathophysiological pathways and identification of new therapeutic intervention strategies for several disorders. Finally, the article gives an overview on the complementary techniques (positron emission tomography, magnetic resonance spectroscopy and open flow microperfusion), and presents their advantages and limitations versus to in vivo MD. In summary, MD techniques have a wide variety of the fields of application. There are several new approaches using this methodology. The relatively low price and the importance of the information gained on the pharmacologically active form of the test articles at the site of interest guarantees a significant position of this technique in the preclinical and clinical research.

Development of a MD-LC-MS/MS Method to Analyze 3 Bioactive Compounds in Huoxuezhitong Rubber Patch and Application to a Pharmacokinetic Study in Rats

“…For water-soluble ingredients, the application of microdialysis technology following transdermal administration has become more mature [33, 34]. As for lipophilic ingredients, the application is greatly limited on account of the adsorption nature of the microdialysis probe.…”

Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic “Skin-On-A-Chip” Microfluidic Device

“…Microdialysis is a minimally invasive in vivo sampling technique which is used for the continuous monitoring of unbound analyte concentrations in the extracellular milieu in different tissues [ 23 ]. In the current study, a transdermal microdialysis technique was applied to investigate the skin penetration of test compounds through the dermal skin layer in anesthetized rats [ 24 ].…”

Skin-on-a-Chip Device for Ex Vivo Monitoring of Transdermal Delivery of Drugs—Design, Fabrication, and Testing

“…Microdialysis is an in vivo sampling technique for monitoring the biochemical changes of the extracellular milieu in different tissues with minimal tissue damage [16]. In vivo transdermal microdialysis was performed according to our previous paper [17].…”