title: In vivo real time non invasive monitoring of brain penetration of chemicals with near-infrared spectroscopy: Concomitant PK/PD analysis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
  
  
  METHODS
  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.
authors.affiliation: Biology Dept, GSK Verona, Verona, Italy. Electronic address: fm.crespi@libero.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Crespi
authors.affiliation: Department of Engineering Enzo Ferrari, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: stefano.cattini@unimore.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cattini
authors.affiliation: Department of Engineering Enzo Ferrari, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: maurizio.donini@unimore.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Donini
authors.affiliation: Department of Engineering Enzo Ferrari, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: andrea.bandera@unimore.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bandera
authors.affiliation: Department of Engineering Enzo Ferrari, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: luigi.rovati@unimore.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Rovati
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002245:Carbon Dioxide / Q000008:administration & dosage; D006454:Hemoglobins / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage; D051381:Rats; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D006454:Hemoglobins; D002245:Carbon Dioxide; D010100:Oxygen
keywords: Brain penetration; CO(2); Hb; HbO(2); In vivo; NIRS; Non invasive; O(2); PK/PD; Rat brain