NDLI: Results and validation of a population pharmacodynamic model for cognitive effects in Alzheimer patients treated with tacrine.

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Methodologic aspects of a population pharmacodynamic model for cognitive effects in Alzheimer patients treated with tacrine.

Results and validation of a population pharmacodynamic model for cognitive effects in Alzheimer patients treated with tacrine.

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Results and validation of a population pharmacodynamic model for cognitive effects in Alzheimer patients treated with tacrine.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Holford, N. H. Peace, K. E.
Spatial Coverage	United States
Description	Author Affiliation: Holford NH ( Department of Pharmacology and Clinical Pharmacology, University of Auckland, New Zealand.);
Abstract	Tacrine has been studied in two clinical trials of identical design in patients with probable Alzheimer disease. One trial enrolled patients in the United States, while the other enrolled patients in France. A population pharmacodynamic model has been used to describe the cognitive component of the Alzheimer disease assessment scale (ADASC) using mixed effects nonlinear regression. The model parameters and their population variability and covariance were estimated by using NONMEM. During an observation period of up to 5 months, the rate of disease progression was 6.17 ADASC units/year. The effect of tacrine was described best by a shift in the disease progress curve (-2.99 ADASC units or 177.6 days at a dose of 80 mg/day). The placebo effects associated with tacrine and placebo treatment were similar in magnitude and time course. There was no evidence of tolerance to tacrine but tolerance to the placebo treatment developed during the study. The size of the placebo effect in the French population was 76% larger than in the United States population, and the response to placebo diminished more slowly in the French population.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	23
Volume Number	89
Language	English
Publisher	National Academy of Sciences
Publisher Date	1992-01-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Alzheimer Disease Drug Therapy Cognition Drug Effects Tacrine Therapeutic Use Double-Blind Method Likelihood Functions Models, Biological Placebo Effect Pharmacology Clinical Trial Randomized Controlled Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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