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|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||Citation:||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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