NoAb BioDiscoveries is a leading research facility located in the heart of one of North America's key biotech hubs and offers a wide range of specialized and proprietary research services that focus on lead selection and optimization in drug discovery research. The facility uses innovation to consistently develop advanced tools and research technologies to better characterize the pharmacokinetic properties of drug candidates, optimizing the selection of viable candidates. By delivering innovative drug discovery research services and tools, NoAb BioDiscoveries facilitates the acceleration of the drug discovery process while still providing accurate and reliable results through superior scientific procedures. Services available from NoAb BioDiscoveries include in vitro ADME assays, in vivo pharmacokinetic studies, bioanalysis and gene expression profiling. Although ADME profiling produces valuable insight into lead selection and optimization, it is still necessary to use in vivo drug exposure to make decisions about molecules within a structural class such as a cerebrospinal fluid drug.
In vivo pharmacokinetic studies at NoAb BioDiscoveries are performed on rats and mice and typically involve fully conscious animals that have been appropriately catheterized for drug administration and sample collection. Skillfully designed assays are performed in-house by highly trained and experienced scientists under strict guidelines ensuring quality, efficiency and timeliness. The pharmacokinetic studies include carotid artery and jugular vein catheterized rats with intra-duodenal dosing, carotid artery, jugular vein and bile duct catheterized rats and guinea pigs, hepatoportal vein catheterized rats, serial collection of plasma and cerebrospinal fluid (CSF) in freely moving rats and microdialysis. Drug penetration into the central nervous system (CNS) is vital when characterizing a CNS-targeted compound for potential efficacy and/or toxicity as in many instances, the concentration of cerebrospinal fluid drug is indicative of its brain concentration. A cerebrospinal fluid drug is a beneficial treatment of neurological and psychiatric disorders where therapeutic targets reside mainly in the CNS.
At NoAb BioDiscoveries, in vivo pharmacokinetics studies for a cerebrospinal fluid drug are conducted based on the ability to examine the time course of the drug in the CSF and plasma following IV administration. Detailed analysis of the cerebrospinal fluid drug by continuous collection of CSF and plasma samples from a single rat over an extended time period of between 6 to 8 hours and the construction of plasma concentration versus time profiles gives an estimation of the brain penetration of the drug candidate. The model consists of freely moving rats which have had cannulas placed into the femoral vein and artery for drug candidate administration and blood sample collection, respectively and a third cannula is inserted into the cisterna magna for CSF collection. Depending on the sensitivity of the bioanalytical method of the drug candidate, the CSF can be collected at between 10-30 minute intervals while the blood sample is collected at the mid-point of each CSF collection interval.
The cerebrospinal fluid drug candidate concentrations in the plasma and CSF are determined by LC-MS/MS methods using state-of-the-art equipment. The assay is an important tool for pre-screening of novel drug candidates in neuropharmacotherapy, brain chemotherapy and antimicrobial therapy for CNS intended use. For an example of a study for a cerebrospinal fluid drug candidate carried out by NoAb BioDiscoveries and more information on this in vivo assay, visit www.noabbiodiscoveries.com.
