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

BACKGROUND: Donepezil is approved for treatment of dementia of the Alzheimer type and is currently available only in tablet forms in the United States. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.