Comparison of Steady-State Pharmacokinetics of Donepezil Transdermal Delivery System with Oral Donepezil.

Abstract

Donepezil is approved for treatment of dementia of the Alzheimer type and is currently available only in tablet forms in the United States. To compare steady-state pharmacokinetics of once-weekly 10-mg/d and 5-mg/d Corplex™ donepezil transdermal delivery systems (TDS) with once-daily 10-mg oral donepezil. Open-label, randomized, crossover study (NCT04617782) enrolled healthy participants aged 18-55 years. All participants received 5-mg/d donepezil TDS during the 5-week Period 1, followed by 10-mg/d TDS or 10-mg/d oral donepezil in the 5-week Period 2; treatments were switched in Period 3. Bioequivalence was assessed at steady state on Week 5. All 60 enrolled participants received 5-mg/d TDS, 55 received 10-mg/d TDS, and 56 received oral donepezil. Adjusted geometric mean ratio (% [90% CI]) for maximum plasma concentration and area under the plasma concentration versus time curve (0-168 h) were 88.7 (81.7-96.2) and 108.6 (100.5-117.4) for 10-mg/d and 86.1 (79.8-92.9) and 105.3 (97.6-113.6) for dose-normalized 5-mg/d TDS and were generally within the 80% -125% range for establishing bioequivalence with oral donepezil. Skin adhesion was similar for both TDSs (>80% of patches remaining ≥75% adhered throughout the wear period). Overall incidence of adverse events (AEs) was similar across treatments. Compared with 10-mg/d TDS, oral donepezil was associated with higher incidence of gastrointestinal and nervous system AEs (14.5% versus 53.6% and 14.5% versus 30.4%, respectively). Donepezil TDSs are bioequivalent to oral donepezil at steady state and have a safety profile that supports their use in treating dementia of the Alzheimer type.