Pharmacokinetic profiles of current therapies for Alzheimer's disease: implications for switching to galantamine.
Although no pharmacologic treatments have been proved to alter the pathology of Alzheimer's disease, acetylcholinesterase inhibitor (AChEI) therapy offers symptomatic improvements in or delays in the progression of cognitive, behavioral, and functional deficits. Tacrine, donepezil, rivastigmine, and galantamine are the best studied agents in this class. These drugs have varying pharmacokinetic, safety, and tolerability profiles that can affect patient outcomes. Specifically, certain metabolic parameters (ie, half-life and route of metabolism/elimination) can affect a drug's tolerability and become important when a switch from one agent to another is contemplated. The mechanism of action of galantamine, the most recently approved AChEI. varies from that of the other AChEIs in that it has allosteric modulating activity at nicotinic receptors in addition to its ability to inhibit acetylcholinesterase. Benefits of this dual mode of action on the effects of the disease have been suggested.
Farlow
M R
MR
Department of Neurology, Indiana University School of Medicine, Indianapolis 46202-5111, USA. mfarlow@iupui.edu
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy*; D002219:Carbamates / Q000009:adverse effects / Q000493:pharmacokinetics; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics*; D000077265:Donepezil; D004347:Drug Interactions; D005702:Galantamine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000493:pharmacokinetics; D048448:Phenylcarbamates; D010880:Piperidines / Q000009:adverse effects / Q000493:pharmacokinetics; D000068836:Rivastigmine; D012890:Sleep / Q000187:drug effects
D002219:Carbamates; D002800:Cholinesterase Inhibitors; D007189:Indans; D048448:Phenylcarbamates; D010880:Piperidines; D005702:Galantamine; D000077265:Donepezil; D000068836:Rivastigmine