Authors: Greig, Nigel H.; Ruckle, Jon; Comer, Patrick; Brownell, Lidia; Holloway, Harold W.; Flanagan Jr., Douglas R.; Canfield, Craig J.; Burford, Robert G.

Source: Current Alzheimer Research, Volume 2, Number 4, October 2005 , pp. 483-492(10)

Publisher: Bentham Science Publishers

Abstract:

Objective: To evaluate the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics (PD) of the acetyl-selective anticholinesterase, phenserine tartrate, in healthy elderly subjects.

Methods: 32 healthy elderly volunteers received single oral doses of phenserine tartrate (5-20 mg). Physical and vital signs were monitored over the ensuing 24 hours. Analyses were performed on plasma samples to determine PK, and PD were assessed using an erythrocyte acetylcholinesterase (AChE) inhibition assay.

Results: No serious adverse events (AEs) occurred; the most common were headache and vomiting. The MTD of phenserine tartrate was 10 mg. The Cmax and AUC(0-24) of phenserine increased with dose, but neither were doseproportional. Subjects receiving 10 mg of phenserine tartrate had a Cmax of 1.95 ng/mL at 1.5 hours, and the mean peak inhibition (Imax) of AChE was 26% (range: 18-34%) at 1.75 hours (tImax) following dosing. The half-life of AChE inhibition (tI1/2) was 11 hours. Evaluation of PK/PD relationships suggested a linear correlation between plasma phenserine concentration and AChE inhibition in the blood.

Conclusions: Phenserine tartrate was safe and well tolerated when administered as a single oral dose of either 5 mg or 10 mg. An increase in the severity and frequency of AEs occurred at the 20 mg dose level.

Keywords: phenserine; anticholinesterase; pharmacokinetics; pharmacodynamics; alzheimers disease; phase clinical trial

Document Type: Review article

DOI: http://dx.doi.org/10.2174/156720505774330564

Affiliations: 1: Room 4B02, 5600 Nathan Shock Dr., Baltimore, MD 21224, USA.

Publication date: 2005-10-01

More about this publication?

• Current Alzheimer Research publishes peer-reviewed frontier review and research articles on all areas of Alzheimer's disease. This multidisciplinary journal will help in understanding the neurobiology, genetics, pathogenesis, and treatment strategies of Alzheimer's disease. The journal publishes objective reviews written by experts and leaders actively engaged in research using cellular, molecular, and animal models. The journal also covers original articles on recent research in fast emerging areas of molecular diagnostics, brain imaging, drug development and discovery, and clinical aspects of Alzheimer's disease. Manuscripts are encouraged that relate to the synergistic mechanism of Alzheimer's disease with other dementia and neurodegenerative disorders. Book reviews, meeting reports and letters-to-the-editor are also published. The journal is essential reading for researchers, educators and physicians with interest in age-related dementia and Alzheimer's disease. Current Alzheimer Research provides a comprehensive 'bird's-eye view' of the current state of Alzheimer's research for neuroscientists, clinicians, health science planners, granting, caregivers and families of this devastating disease.

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• By this author: Greig, Nigel H. ;  Ruckle, Jon ;  Comer, Patrick ;  Brownell, Lidia ;  Holloway, Harold W. ;  Flanagan Jr., Douglas R. ;  Canfield, Craig J. ;  Burford, Robert G.

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