Dear Madam / Sir,Back to the Top
I enjoyed very much the discussion on brain penetration models. I am
looking for a good in vivo techniqueto study brain penetration of
drugs in rats (not microdialysis). I searched the references mentioned
in the PharmaPK discussion, but I still have not found a proper
protocol (dosing, tracer, surgical removal of the brain, washing,
homogenization, etc.).
Looking forward to your answer,
Yours sincerely,
Gyula
Dear Gyula,Back to the Top
look in the following articles:
Zlokovic et al, 1986, J Neurochem, 46, 1444-1459
Takasato et al, 1984, Am J Physiol, 247, H484-H493
Best regards,
Suzana Corritori, MD, PhD
Director, Drug Development
Avanir Pharmaceuticals
San Diego, CA
Dear GyulaBack to the Top
Try this article on Brain and plasma exposure profiling in early
discovery.
Mei-Yi Zhang et al.
Journal of Pharmaceutical and Biomedical Analysis 34 (2004) 359-368
Best regards
Eva Dam
Neurosearch
Denmark
Dear GyulaBack to the Top
Brain penetration of drugs cannot be assessed with 'expedient'
radioassays or whole-body autoradiography, nor with scanning
procedures, nor with dialysis.
As Lloyd Roth once stated: "Don't homogenize the brain. The brain you
are homogenizing may be your own."
In vivo assessment of drug penetration requires techniques with high
sensitivity and high resolution, such as Receptor Microautoradiography
(http://www.unc.edu./~stumpfwe). I have discussed this topic in the
cited publication.
Drugs may be located at specific cell populations that are not
recognized in whole brain preparations. There are many false negatives
published in the literature. For insdtance: Brain and spinal cord
distribution of vitamin D is reported to be negative with radioassay-
HPLC and whole-body autoradiography. However, with our receptor
microautoradiography technique, we have been able to detect many
target cell populations and published maps of specific neuronal target
circuits in brain and spinal cord.
Walter E. Stumpf
Chapel Hill, NC
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