Background. Near-infrared spectroscopy (NIRS) is a non-invasive technique that monitors changes in oxygenation of haemoglobin. The absorption spectra of near-infrared light differ for the oxygenation–deoxygenation states of haemoglobin (oxygenate (HbO2) and deoxygenate (Hb), respectively) so that these two states can be directly monitored. Comparison with existing method(s). Different methodologies report different basal values of HbO2 and Hb absolute concentrations in brain. Here, we attempt to calculate basal HbO2 levels in rat CNS via evaluation of the influence of exogenous oxygen or exogenous carbon dioxide on the NIRS parameters measured in vivo. New method. Furthermore the possibility that changes of haemoglobin oxygenation in rat brain as measured by NIRS might be a useful index of brain penetration of chemical entities has been investigated. Different compounds from different chemical classes were selected on the basis of parallel ex vivo and in vivo pharmacokinetic (PK/PD) studies of brain penetration and overall pharmacokinetic profile. Results. It appeared that NIRS might contribute to assess brain penetration of chemical entities, i.e. significant changes in NIRS signals could be related to brain exposure, conversely the lack of significant changes in relevant NIRS parameters could be indicative of low brain exposure. Conclusions. This work is proposing a further innovation on NIRS preclinical applications i.e. a “chemical” NIRS [chNIRS] approach for determining penetration of drugs in animal brain. Therefore, chNIRS could became a non invasive methodology for studies on neurobiological processes and psychiatric diseases in preclinical but also a translational strategy from preclinical to clinical investigations.
|Data di pubblicazione:||2015|
|Titolo:||In vivo real time non invasive monitoring of brain penetration of chemicals with near-infrared spectroscopy: Concomitant PK/PD analysis|
|Autori:||Crespi, Francesco; Cattini, Stefano; Donini, Maurizio; Bandera, Andrea; Rovati, Luigi|
|Digital Object Identifier (DOI):||10.1016/j.jneumeth.2015.10.011|
|Appare nelle tipologie:||Articolo su rivista|
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