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 (1.5-6mg Q12H, i.e., 3-12 mg/day) or patch (5-20 cm(2)) in ascending doses through four 14-day periods. The patch showed lower C-max (ca. 30% lower at 20 cm(2), 19.5 versus 29.3 ng/ml), longer t(max) (8.0 versus 1.0 h), and greater AUC (ca. 1.8-fold at 20 cm(2), 345 versus 191 ng. h/ml) compared with the 6 mg Q12H capsule dose, with markedly less fluctuation between peak and trough plasma levels (80% at 20 cm(2) versus 620% at 1.5mg Q12H). Plasma butyrylcholinesterase inhibition rose slowly after patch administration, whereas two distinct peaks were seen after capsule administration. Average exposure with the 10 cm 2 patch was comparable to the highest capsule dose (6 mg Q12H, i.e., 12mg/day).