Steady-state pharmacokinetics of rivastigmine in patients with mild to moderate Alzheimer's disease not affected by co-administration of memantine: an open-label, crossover, single-centre study.
OBJECTIVE
It has been shown that combining memantine and a cholinesterase inhibitor, which each affect different neurotransmitter systems, may offer further improvements in efficacy over either treatment alone in patients with Alzheimer's disease. The present study was conducted to determine if memantine has any effects on the steady-state pharmacokinetics of rivastigmine in patients with mild to moderate Alzheimer's disease.


METHODS
Rivastigmine-treated Alzheimer's disease patients who had been maintained on a fixed regimen of twice-daily rivastigmine for >or=2 months were eligible to enter the study. Sixteen patients (seven males and nine females, age range 64-88 years, weight range 51.8-104 kg) were enrolled in this open-label, crossover study, which consisted of a 28-day screening period, a 36-hour baseline period, and a 35-day combination treatment phase. The patients spent the baseline period and day 35 at the study centre, where plasma samples for pharmacokinetic evaluation were taken at specified time intervals over a 10-hour time period. In addition, 10-hour (evening pre-dose) memantine plasma samples were taken on days 21, 34 and 35.


RESULTS
The combination of memantine (10 mg twice daily) with rivastigmine (1.5-6 mg twice daily) was safe and well tolerated. At each dose level of rivastigmine, the area under the concentration-time curve (AUC) values of rivastigmine and its metabolite as well as the metabolite-to-parent AUC ratios were unaffected by co-administration of memantine, confirming the absence of a meaningful pharmacokinetic drug-drug interaction.


CONCLUSIONS
Under the study conditions, the extent of systemic exposure to rivastigmine and its metabolite NAP226-90 at steady state did not appear to be affected by concomitant administration of memantine.
Shua-Haim
Joshua
J
Memory Disorders Institute, Meridian Institute for Aging, Affiliated with Meridian Health System and Jersey Shore Medical Center, Neptune, New Jersey, USA.
Smith
Juanita
J
Picard
Franck
F
Sedek
Greg
G
Athalye
Sandeep
S
Pommier
Françoise
F
Lefèvre
Gilbert
G
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy*; D019540:Area Under Curve; D001596:Benzylamines / Q000493:pharmacokinetics; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008559:Memantine / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010627:Phenethylamines; D010636:Phenols / Q000493:pharmacokinetics; D048448:Phenylcarbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068836:Rivastigmine
C494046:3-(1-dimethylaminoethyl)phenol; D001596:Benzylamines; D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D010627:Phenethylamines; D010636:Phenols; D048448:Phenylcarbamates; D000068836:Rivastigmine; D008559:Memantine