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Brain Tissue Binding

Creative Animodel offers a fast high throughput method to estimate brain tissue binding on drugs and predict their dispositions in brain. We can deliver consistent and high-quality data with flexibility to adapt protocols based on customers’ requirements.

Why Is Brain Tissue Binding Important?

The central nervous system (CNS) is an extravascular compartment and not directly accessed from the systemic circulation because of the blood-brain barrier (BBB). For a compound to reach a target in the CNS, the free drug in plasma must first cross this barrier. According to the “free drug hypothesis”, if a compound reaches the brain by passive diffusion in blood, the unbound concentration in the brain (Cu,b) at steady state corresponds to the unbound concentration in plasma (Cu,p). However, if a compound is actively transported across the BBB, Cu,b deviates from Cu,p as a result of a concentration gradient maintained by the transporter protein; Cu,b can then no longer
be derived solely from the plasma concentration. In this case, a straightforward method to reliably estimate unbound drug concentrations in the brain is essential. For neuroscience therapeutic targets, accurate understanding of total and free drug concentrations in brain is critical for developing PK/PD relationships, projecting doses and designing clinical studies.

Our Brain Tissue Binding Assay

For brain tissue binding, both standard and high throughput methods using brain homogenates have been developed to determine the fraction unbound (fu) of drugs in brain tissues at Creative Animodel. Good predictability and ease of use make brain homogenate binding one of the most widely used methods for determining fraction unbound in brain tissues. Our assays are accomplished by following three steps: preparation of brain homogenates, equilibrium dialysis for brain binding study and calculation of fraction unbound.

Calculation of Fraction Unbound. fu is calculated using equipments. Because unbound fractions determined from diluted brain homogenates are higher than those from undiluted brain tissue, corrections are made on the basis of the dilution factor (D). Masses in receiver and donor are determined from the area counts in these samples obtained from LC-tandem mass spectrometry analysis corrected to account for sampling volumes. A dilution factor of 5 (D=5) is applied in the calculation that reflects the dilution of the brain tissue homogenates.

Our Advantages
• High throughput and ease of handling
• Low cost and with less resources needed
• Behavior difference monitering between species

Creative Animodel has experienced experts in the field of preclinical drug evaluation. If you have any questions, please feel free to contact us.

Reference:
1. Di L.; et al. Species independence in brain tissue binding using brain homogenates. Drug Metabolism & Disposition the Biological Fate of Chemicals. 2011, 39(7):1270.

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45-1 Ramsey Road, Shirley, NY 11967, USA 1-631-207-8356 1-631-871-5806 Europe 44-207-097-1828

Creative Animodel

Creative Animodel is a world's leading commercial provider of custom animal model services. We offer top-quality services at unbeatable prices. Our customer service representatives are available 24 hours a day, from Monday to Sunday.

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