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Related Experiment Video

Updated: Jun 3, 2026

Isolation of Cerebral Capillaries from Fresh Human Brain Tissue
06:35

Isolation of Cerebral Capillaries from Fresh Human Brain Tissue

Published on: September 12, 2018

Species independence in brain tissue binding using brain homogenates.

Li Di1, John P Umland, George Chang

  • 1Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Eastern Point Rd., Groton, CT 06340, USA. li.di@pfizer.com

Drug Metabolism and Disposition: the Biological Fate of Chemicals
|April 9, 2011
PubMed
Summary

Brain tissue binding of drug compounds is highly consistent across seven species and strains. Wistar Han rat data accurately predicts binding in other species, simplifying drug discovery.

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Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Neuroscience
  • Toxicology

Background:

  • Understanding drug distribution in the brain is crucial for predicting efficacy and toxicity.
  • Species-specific differences in drug binding can complicate preclinical to clinical translation.

Purpose of the Study:

  • To assess the species independence of brain tissue binding for structurally diverse compounds.
  • To determine if Wistar Han rat brain homogenates can serve as a reliable model for predicting binding in other species and strains relevant to drug discovery.

Main Methods:

  • Equilibrium dialysis was employed to measure the unbound fraction of compounds in brain homogenates.
  • Seven species and strains were utilized: Wistar Han rat, Sprague-Dawley rat, CD-1 mouse, Hartley guinea pig, beagle dog, cynomolgus monkey, and human.

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  • Orthogonal statistical analysis was performed to evaluate cross-species correlations.

    • Main Results:

    • High correlations (0.93–0.99) were observed between unbound fractions across all seven species and strains.
    • Cross-species/strain correlations were comparable to interassay correlations within the same species.
    • Linear regression analysis between Wistar Han rat and other species showed slopes near 1 and intercepts near 0.

    Conclusions:

    • Brain tissue binding is largely species-independent for the tested compounds.
    • Wistar Han rat brain homogenates provide a predictive model for brain tissue binding across multiple species and strains.
    • No correction factors are necessary for extrapolating Wistar Han rat unbound fraction data to other species, streamlining drug discovery efforts.