Pharmacokinetics and pharmacodynamics of the novel daily rivastigmine transdermal patch compared with twice-daily capsules in Alzheimer's disease patients.
A transdermal patch has been developed for the cholinesterase inhibitor rivastigmine. This study investigated the pharmacokinetics and pharmacodynamics of rivastigmine and NAP226-90, and compared drug exposure between patch and capsule administrations. This was an open-label, parallel-group study in Alzheimer's disease patients randomized to receive either capsule (1.5-6 mg Q12H, i.e., 3-12 mg/day) or patch (5-20 cm2) in ascending doses through four 14-day periods. The patch showed lower Cmax (ca. 30% lower at 20 cm2, 19.5 versus 29.3 ng/ml), longer tmax (8.0 versus 1.0 h), and greater AUC (ca. 1.8-fold at 20 cm2, 345 versus 191 ng x h/ml) compared with the 6 mg Q12H capsule dose, with markedly less fluctuation between peak and trough plasma levels (80% at 20 cm2 versus 620% at 1.5 mg Q12H). Plasma butyrylcholinesterase inhibition rose slowly after patch administration, whereas two distinct peaks were seen after capsule administration. Average exposure with the 10 cm2 patch was comparable to the highest capsule dose (6 mg Q12H, i.e., 12 mg/day).
Lefèvre
G
G
Novartis Pharma AG, Basel, Switzerland. gilbert.lefevre@novartis.com
Sedek
G
G
Jhee
S S
SS
Leibowitz
M T
MT
Huang
H-La
HL
Enz
A
A
Maton
S
S
Ereshefsky
L
L
Pommier
F
F
Schmidli
H
H
Appel-Dingemanse
S
S
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D001596:Benzylamines / Q000493:pharmacokinetics; D002091:Butyrylcholinesterase / Q000097:blood; D002214:Capsules; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010627:Phenethylamines; D010636:Phenols / Q000493:pharmacokinetics; D048448:Phenylcarbamates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000068836:Rivastigmine; D016896:Treatment Outcome
C494046:3-(1-dimethylaminoethyl)phenol; D001596:Benzylamines; D002214:Capsules; D002800:Cholinesterase Inhibitors; D010627:Phenethylamines; D010636:Phenols; D048448:Phenylcarbamates; D002091:Butyrylcholinesterase; D000068836:Rivastigmine