Pharmacokinetic
rationale for switching from donepezil to galantamine.
Maelicke, A
Laboratory of Molecular Neurobiology
Johannes-Gutenberg University
Medical School
Mainz, Germany. alfred.maelicke@uni-mainz.de
Clin Ther 2001;23 Suppl A:A8-12
ABSTRACT
Galantamine, the most recently approved acetylcholinesterase inhibitor
(AChEI)
for use in the United States, has allosteric modulating activity at
nicotinic receptors and inhibits acetylcholinesterase. This dual
mechanism of action may make galantamine an attractive option for
patients with Alzheimer's disease who have not benefited from their
current therapy; thus, methods for switching patients from donepezil or
rivastigmine to galantamine are needed. Protocols for switching patients
from one AChEI to another must consider both the time required for
washout of the first drug and the rate of dose escalation of the second
drug. Both issues depend on the pharmacodynamics, pharmacokinetics, and
pharmacology of the drugs under consideration. Because the common
property of the drugs considered here is their acetylcholinesterase
inhibitory activity, it seems reasonable to keep this activity at or
below the activity achieved by the first drug at all times. In addition,
the patient's condition should be monitored to avoid deterioration
resulting from subtherapeutic drug concentrations during the switch.
The
switching protocol proposed here has been based on an analysis of mean
plasma concentrations of donepezil following administration of a single
dose and on the established pharmacokinetics of galantamine.
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