CNS Drug Disposition

InterVivo Solutions is committed to improving the success of new drugs by offering translational models and transformative research services. For CNS targeted therapeutics, the disposition of a drug in the brain is a vital factor in understanding its efficacy and safety profile. With a combination of state-of-the-art techniques and extensive CNS development expertise, InterVivo is able to provide support for critical lead selection and development decisions, thereby helping improve the quality of clinical candidates. Techniques employed include:

  • Simultaneous collection of brain tissue and plasma from the same animal followed by LC-MS/MS bioanalysis of compound concentrations
  • Brain and plasma free-fraction determination using equilibrium dialysis
  • Useful for early-stage screening and lead selection programs, and can be combined with efficacy or POC studies
  • Non-survival sampling of cerebrospinal fluid from the cisterna magna of mice can be used to estimate free drug concentrations in the brain following drug administration 1
  • Can be combined with brain tissue harvesting and plasma collection to understand differences in drug exposure for CSF, brain and plasma
  • Also useful as an addition to efficacy or POC studies

1 1. Fan, J. et. al. Drug Metabolism Reviews.44(S1):138-139 (2012)

  • Collecting serial samples of CSF and plasma via surgically implanted catheters allows the determination of unbound drug delivery into the brain in awake rats
  • Reduced inter-animal variability improves quality and power of data over parallel sampling techniques
  • Studies can be performed in SAGE® ADME knockout rats to investigate how specific drug transporters affect the pharmacokinetics of drugs
  • Data rich study designs have demonstrated predictive validity in characterizing drug delivery into the brain 1

1 1. Fan, J. et. al. Drug Metabolism Reviews.44(S1):138-139 (2012)

  • ~150 beagle dogs of various ages are available for CSF and plasma sampling studies to evaluate drug delivery and exposure in a clinically relevant non-rodent species
  • Efficacy and safety profiles of new drugs can be further characterized by assessing drug or biomarker levels in CSF and plasma from the same animal over time
  • Aged dogs provide a natural and translational model for various age related conditions such as Alzheimer’s Disease progression, Osteoarthritis and Cancer
  • Industry accepted gold-standard model for determining unbound drug concentrations in specific brain regions over time
  • Combined drug and biomarker assessment enables PK-PD studies to establish robust dose-response profiles
  • In vitro and in vivo parameters are optimized for each compound to ensure accuracy and reliability of results which can be used to support development decisions.