Pharmacokinetics and Pharmacodynamics of the Novel Daily Rivastigmine Transdermal Patch Compared With Twice-daily Capsules in Alzheimer's Disease Patients

Abstract

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).

Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats

“…2, the trough concentration range after oral administration was wider than after patch administration, which may be associated with the gastrointestinal tract (effects of pH, motility, transit time and food intake). According to previous reports [16][17][18][19], interindividual variation (mean CV) of C max after patch administration was generally smaller than that after oral administration. In the multiple-dose study, the CV of C max after patch administration was smaller than oral administration (oral versus patch administration, 54.92 versus 13.33%).…”

Randomized, Double-Blind, Parallel-Group, 48-Week Study for Efficacy and Safety of a Higher-Dose Rivastigmine Patch (15 vs. 10 cm2) in Alzheimer’s Disease

“…Both rivastigmine formulations are also widely approved for the treatment of Parkinson's disease dementia [12,13]. Previous pharmacokinetic studies have demonstrated that once daily transdermal administration of rivastigmine provides continuous drug delivery, reducing fluctuations in drug plasma concentration, with improved tolerability compared with twice daily rivastigmine capsules [14][15][16]. A large, 24-week, randomized, multicentre, placebo-controlled, double-blind (DB) clinical study (IDEAL; Investigation of transDermal Exelon in ALzheimer's disease) established the 9.5 mg/24 h (10 cm 2 ) rivastigmine patch as the currently recommended target maintenance dose in the treatment of patients with mild-to-moderate AD [8].…”

Characteristics of the clinical picture and treatment of moderate or severe Alzheimer’s disease

“…Разработка пластыря с ривастигми-ном стала возможной благодаря низкой молекуляр-ной массе, а также жиро-и водорастворимым свой-ствам молекулы, что способствовало свободному поступ лению препарата через кожу и гематоэнцефа-лический барьер [11]. Благодаря снижению пика до-зы и меньшему влиянию при трансдермальном вве-дении на циркадный ритм выработки холинэстера-зы, применение ТТС с ривастигмином почти на 2 / 3 позволило снизить частоту гастроинтестинальных побочных эффектов по сравнению с пероральным приемом, при сопоставимом клиническом эффекте [12][13][14].…”