Pharmacokinetic comparison of orally disintegrating and conventional donepezil formulations in healthy Korean male subjects: a single-dose, randomized, open-label, 2-sequence, 2-period crossover study.

摘要: Abstract Background Donepezil is a potent inhibitor of acetylcholinesterase, an enzyme that targeted in the treatment Alzheimer's disease. Objective The purpose this study was to compare pharmacokinetic characteristics orally disintegrating (test) and conventional (reference) donepezil formulations satisfy regulatory requirement for marketing. Methods A single-center randomized, single-dose, open-label, 2-way crossover with 21-day washout period conducted 22 healthy volunteers. Plasma samples analysis were collected up 240 hours after drug administration. Participants received either reference or test formulation 10 mg first alternative second period. concentrations determined by validated high-performance liquid chromatography coupled tandem mass spectrometry detection. Pharmacokinetic parameters, including C max AUC, noncompartmental analysis. ANOVA carried out using log-transformed mean ratios their 90% CIs calculated. safety profiles tolerabilities 2 also assessed based on laboratory tests, 12-lead ECGs, vital signs, physical examinations. Results Of participants initially enrolled, 18 Korean completed both periods. Four subjects did not complete treatments: 3 withdrew consent personal reasons, 1 subject experienced adverse events. No significant differences parameters between observed. (SD) age, height, weight 25.8 (4.1) years, 173.6 (5.7) cm, 68.9 (7.8) kg, respectively. , AUC last inf 33.26 (6.58) ng/mL, 1521.69 (344.04) ng × h/mL, 1691.46 (443.05) Corresponding values 34.23 (6.79) 1554.33 (390.23) 1718.27 (447.03) median T (range, 1–3 hours) formulations. geometric (90% CI) 102.9 (96.8–109.5) 102.3 (96.1–108.9) 101.6 (95.4–108.2) 0–∞ During study, 15 14 events reported formulations, respectively, all transient, mild, resolved during These included 7 cases nausea, headache, case each dizziness, vomiting, chills, sweating. All considered related drugs. Conclusion This found met criteria equivalence these fasting male subjects. Both appeared be generally well tolerated. ClinicalTrials.gov indentifier: NCT01297036 .