Microdialysis as an Important Technique in Systems Pharmacology—a Historical and Methodological Review

Abstract

Abstract.Microdialysis has contributed with very important knowledge to the understanding of target-specific concentrations and their relationship to pharmacodynamic effects from a systems pharmacology perspective, aiding in the global understanding of drug effects. This review focuses on the historical development of microdialysis as a method to quantify the pharmacologically very important unbound tissue concentrations and of recent findings relating to modeling microdialysis data to extrapolate from rodents to humans, understanding distribution of drugs in different tissues and disease conditions. Quantitative microdialysis developed very rapidly during the early 1990s. Method development was in focus in the early years including development of quantitative microdialysis, to be able to estimate true extracellular concentrations. Microdialysis has significantly contributed to the understanding of active transport at the blood-brain barrier and in other organs. Examples are presented where microdialysis together with modeling has increased the knowledge on tissue distribution between species, in overweight patients and in tumors, and in metabolite contribution to drug effects. More integrated metabolomic studies are still sparse within the microdialysis field, although a great potential for tissue and disease-specific measurements is evident.

Concentrations of Cefuroxime in Brain Tissue of Neurointensive Care Patients

“…Furthermore, differences in local perfusion cannot be excluded, even though the probe was always inserted at the same point and depth. To minimize local tissue reaction and potential leakage of the blood-brain barrier caused by the probe insertion, sampling was started at the earliest 1 day after probe implantation, as stated elsewhere (41). Measurement of cefuroxime concentrations was performed in macroscopically noninflamed cerebral tissue.…”

The effects of flaxseed and tamoxifen on the inflammatory microenvironment in normal breast tissue and in breast cancer

“…The collected microdialysate reflects the composition of the extracellular fluid and the analyte concentration in the dialysate is a relative measure of the concentration in the extracellular fluid ( Figure 6) (228). The sampling of a certain molecule is dependent on the flow rate, pore size and the length of the semi-permeable membrane of the catheter to reach equilibrium (229,230). The technique has been extensively used in numerous studies and has proven to be an important method for a greater understanding of pharmacokinetics and metabolism in different tissue (230).…”

“…The sampling of a certain molecule is dependent on the flow rate, pore size and the length of the semi-permeable membrane of the catheter to reach equilibrium (229,230). The technique has been extensively used in numerous studies and has proven to be an important method for a greater understanding of pharmacokinetics and metabolism in different tissue (230). Moreover, microdialysis reflects the concentration of molecules/proteins at the site of interest better than measurements in blood (231,232).…”

A microdialysis perspective of soil nitrogen availability

“…An alternative approach may be to shift our focus towards estimating in situ concentrations using calibration techniques, as done in many biomedical studies (Kho et al, 2017, Bourne, 2003, Hammarlund-Udenaes, 2017. Given that most conventional methods of sampling soil solutes provide absolute concentrations (not fluxes), estimating in situ solute concentrations may provide an avenue for better comparisons across soils studies.…”

“…Microdialysis is a passive sampling technique initially developed for biomedical research and used extensively in neurology, pharmokinetics and pathology (Bourne, 2003, Hammarlund-Udenaes, 2017, Nandi and Lunte, 2009. It remains as one of the only tools capable of high-resolution sampling of target solutes in vivo, in part due to the minimal disruption imparted to surrounding tissue structures, and the passive nature of the sampling process (Nandi and Lunte, 2009).…”