Exclusion of unsuitable CNS drug candidates based on their physicochemical properties and unbound fractions in biomatrices for brain microdialysis investigations

Publication date: Available online 25 October 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Qianwen Wang, Tianjing Ren, Jiajia Zhao, Chun-Ho Wong, H.Y. Edwin Chan, Zhong ZuoAbstractMicrodialysis has been the only direct method of continuously measuring the unbound drug concentrations in extracellular fluid at a specific brain region with respect to time in the same animal. However, not every compound is suitable for microdialysis system as demonstrated by their inconsistent “by gain” and “by loss” in-vitro microdialysis probe recoveries leading to over- or under- estimated in-vivo concentrations. Therefore, our current study was proposed aiming to develop simple exclusion criteria for drug candidates that are not suitable for microdialysis system investigation. Through literature research, the properties ((LogP, pKa, water solubility and unbound fraction in plasma and brain) of drugs that have been reported for microdialysis studies were summarized. The exclusion criteria were developed by evaluating the impact of such properties on the consistency of in-vitro “by gain” and “by loss” recoveries of microdialysis probe. As a result, forty-five compounds were identified from literatures, among which doxorubicin, docetaxel, omeprazole, donepezil and phenytoin were found to have inconsistent in-vitro “by gain” and “by loss” microdialysis probe recoveries and subsequently selected for the exclusion criteria analysis. It was found th...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research