Intracerebral microdialysis technique and its application on brain pharmacokinetic-pharmacodynamic study

Abstract

Intracerebral microdialysis (IC-MD) has been developed as a well-validated and powerful technique for decades. As a practical sampling tool, it can gain the continuous dialysates of endogenous and exogenous substances in extracellular fluid (ECF) of awake freely moving animals. Also, variform IC-MD probes (IC-MDPs) have grown more exquisite. The implantation of the IC-MDP in certain tissue of brain allows monitor drug distribution and measure drug and corresponding neurotransmitters levels in brain ECF after administration for brain pharmacokinetic-pharmacodynamic (B-PK-PD) study. So it is suitable for IC-MD to B-PK-PD study (IC-MD/B-PK-PD). The performance of IC-MD/B-PK-PD can not only elevate the degree of precision and accuracy of experimental data, minimize the individual difference by reduced number of animals, but also give important information for the prediction and optimization of drug effective dose in preclinical study. In this review, we have discussed various IC-MD/B-PK-PD studies of analgesic, antiepileptic and antidepressant drug. The role of IC-MD/B-PK-PD in confirming and assessing the drug effect before clinic trials is highlighted.

Effects on sleep and dopamine levels of microdialysis perfusion of cannabidiol into the lateral hypothalamus of rats

“…Since this experimental approach mimics the function of a capillary blood vessel by perfusing soluble molecules from a semipermeable membrane in the tip of the probe, represents a reliable technique. Additionally, on preclinical studies, microdialysis strength the understanding of pharmacological properties of novel drugs on certain functions of the central nervous system (de Lang et al 2005;Danhof et al 2005;Li et al 2006;Pan et al 2007). We can suggest that the perfusion of CBD during 1 h via microdialysis allowed the understanding of the relationship among the effects of this compound and the physiological changes occurring on sleep as well as the effects on the endogenous concentration of DA.…”

Concentrations of Cefuroxime in Brain Tissue of Neurointensive Care Patients

“…The usefulness of this technique in neurointensive care units for patients suffering from head injury or subarachnoid hemorrhage has been reported in previous research (13,14). In addition, cerebral microdialysis enables the measurement of free interstitial antibiotic concentrations within the brain tissue of a concomitant systemic antibiotic treatment, without the need for further invasive study-related procedures (15)(16)(17)(18).…”

Magnetic Resonance Imaging–Guided Microdialysis Cannula Implantation in a Spontaneous High-Grade Glioma Murine Model

“…This approach provides advantages over other sampling methods (e.g., whole tissue homogenization) including sampling from discrete anatomic compartments such as the brain extracellular fluid or ventricular cerebrospinal fluid,3 sampling from normal brain or brain tumor tissue, and acquisition of unbound or pharmacologically active drug moieties 4. Furthermore, microdialysis enables serial sampling from individual animals, thereby reducing the number of animals required for pharmacokinetic investigations 5…”