Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/17712
Title: Investigating the influence of Age on Pharmacokinetic and Pharmacodynamic characteristics of Gold standard Alzheimer's Disease drugs in the lister - Hooded Rat.
Authors: GOH WENHUI, CATHERINE
Keywords: ageing,lister-hooded,cholinesterase inhibitors,alzheimer's disease,pharmacokinetics,pharmacodynamics
Issue Date: 7-Aug-2009
Source: GOH WENHUI, CATHERINE (2009-08-07). Investigating the influence of Age on Pharmacokinetic and Pharmacodynamic characteristics of Gold standard Alzheimer's Disease drugs in the lister - Hooded Rat.. ScholarBank@NUS Repository.
Abstract: Ageing accompanies physiological alterations that may change pharmacological response. PK/PD properties of AD drugs Aricept, Tacrine, Galantamine, and Memantine, were investigated in an aged Lister-hooded rat model. Intravenous and oral 6h blood-sampling profiles in old (30-months) and young (7-months) rats revealed similar PK changes to humans with significant increase in Cmax of Galantamine and prolonged half-life of Aricept. A trend of slightly decreased clearance was seen for all drugs, correlating with a reduction of CYP1A and 3A activity with age, although bioavailability remained unchanged. Brain:blood ratios of the drugs were maintained in old rats supported by unchanged brain P-glycoprotein mRNA expression. Old rats reported increased PD sensitivity to cholinesterase inhibitors (ChEIs) which was attributed to PK effects and decreased muscarinic acetylcholine receptor subtype 2 expression. Similar PK/PD studies of ChEIs with Fischer344 rats saw greater age effects, indicating a potential risk in over-reliance of a single strain for ageing studies.
URI: http://scholarbank.nus.edu.sg/handle/10635/17712
Appears in Collections:Master's Theses (Open)

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