Pharmacokinetic rationale for switching from donepezil to galantamine

Abstract

Galantamine, the most recently approved acetylcholinesterase inhibitor (AChEI) for usein 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.