Increased plasma donepezil concentration improves cognitive function in patients with dementia with Lewy bodies: An exploratory pharmacokinetic/pharmacodynamic analysis in a phase 3 randomized controlled trial
التفاصيل البيبلوغرافية
العنوان:
Increased plasma donepezil concentration improves cognitive function in patients with dementia with Lewy bodies: An exploratory pharmacokinetic/pharmacodynamic analysis in a phase 3 randomized controlled trial
ObjectiveTo investigate whether increasing plasma donepezil concentration further improves cognitive function and neuropsychiatric symptoms without compromising safety in patients with dementia with Lewy bodies (DLB).MethodsWe analyzed data from a 12-week phase 3 trial of donepezil (5 and 10mg/day) in patients with DLB. The contribution of factors affecting plasma donepezil concentration was evaluated using multivariate regression analysis. The relationships between plasma donepezil concentration and efficacy (cognitive function as measured by the Mini-Mental State Examination [MMSE], hallucinations and cognitive fluctuation), or safety (blood pressure, pulse rate, body weight, and parkinsonism as measured by the Unified Parkinson's Disease Rating Scale part III) were assessed by scatterplots and Pearson correlation.ResultsThe data of 87 patients were used in the analyses. Plasma donepezil concentration increased proportionally with increasing dose from 5 to 10mg/day. The dose (contribution rate: 0.39, p
