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P4‐254: A novel medical food Souvenaid® for AD patients can be used safely in combination with an acetylcholinesterase inhibitor in an aged rat model
Author(s) -
Wilde Martijn,
Wijk Nick,
Kuipers Almar,
Broersen Laus,
Kamphuis Patrick,
Garthoff Jossie,
Speijers Gerrit
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.2279
Subject(s) - acetylcholinesterase , urination , aché , cholinergic , adverse effect , medicine , pharmacology , acetylcholinesterase inhibitor , chemistry , biochemistry , enzyme , urinary system
in the NHP were performed following iv bolus and infusion treatment with SAM-760 designed to maintain steady state drug exposure throughout the experiment. Human PET RO was evaluated at approximately tmax and 24 or 48h following oral treatment with a single dose of SAM-760. All animal study procedures conducted were approved by an institutional review committee (IACUC). Results: [C] GSK215083 produced reproducible test-retest values in both species (NHP: caudate 1⁄4 15.0 6 6.8%, putamen 1⁄4 12.1 6 7.3%; human: caudate 1⁄4 19.8 6 10.6%, putamen 1⁄4 16.6 6 12.7%). In the NHP, SAM760 treatment produced exposure dependent RO in the striatum, with a complete blockade of the receptor at free drug plasma exposures of > 10 nM. Human RO studies with SAM-760 demonstrated RO within the striatum of > 70% following treatment with a single oral dose of 60 mg. Conclusions: The PET radiotracer [C]GSK215083 demonstrated robust test-retest reliability within striatal structures for both species. Characterization of the RO: exposure relationship for SAM-760 in NHP and human striatum demonstrated that high levels of RO can be achieved at clinically relevant drug exposures. These studies provide support for dose selection for the further development of SAM-760 as a potential treatment for the cognitive deficits associated with Alzheimer’s disease.