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Biodistribution Processes as Underestimated Confounders in Translational Stroke Research

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Abstract:

Pharmacological therapies in ischemic stroke have made limited progress in recent years. After many negative neuroprotection trials in humans, considerable concerns have been raised about future research strategies. This led to expert rounds, the so-called STAIR conferences, which critically reviewed previous studies and provided research recommendations. Hopes were raised that STAIR might lead to breakthroughs in neuroprotection strategies in the near future. Whether this will indeed become true, remains to be awaited. An important aspect in the context of brain pharmacotherapies is the blood-brain barrier, which prevents drugs from brain entrance. The blood-brain barrier not only acts as passive diffusion barrier, it expresses active transporters that eliminate drugs from the brain and thereby profoundly influence drug tissue levels. These transporters exhibit strong variabilities between animals and humans, which make it hardly possible to predict brain concentrations of drugs over species barriers. As such, drug biodistribution turns out to be a major confounder in pharmacological therapies. This paper claims that more precise brain accumulation studies are needed in preparation for clinical trials both in animals and in humans. This might lead to better dose selections and higher success rates of future pharmacological trials.





Keywords: ABC transporter; focal cerebral ischemia; pharmacology

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707782793817

Publication date: December 1, 2007

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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