Daiichi Sankyo Co., Ltd., Tokyo, Japan.
Pharmaspur Inc., Tokyo, Japan.
Adv Ther. 2019 Oct;36(10):2930-2940. doi: 10.1007/s12325-019-01044-y. Epub 2019 Aug 9.
Memantine hydrochloride, an N-methyl-D-aspartate receptor antagonist, is used to treat Alzheimer's disease (AD). A new dry syrup formulation containing memantine hydrochloride has been developed to improve medication adherence in AD patients and to reduce family and caregiver burden. This study was conducted to assess the bioequivalence of this new formulation to the tablet.
Two single-dose, randomized, open-label, two-period, two-group, crossover studies were conducted to assess the bioequivalence of a test product [dry syrup, 2%, 1 g (containing 20 mg of memantine hydrochloride)] to a reference product (film-coated tablet) under two dosing conditions: administration of the test product as a suspension in water (Study I) and as granules taken with water (Study II). Blood samples were collected at specified time intervals, and memantine plasma concentrations were determined using a validated liquid chromatography tandem mass spectrometry method. The pharmacokinetic parameters of memantine were calculated using non-compartmental analysis. The maximum concentration (C) and area under the concentration-time curve up to the last sampling time (AUC) were used to assess the bioequivalence of the two formulations.
The geometric least square mean (GLSM) ratios [90% confidence interval (CI)] of the C and AUC of memantine for the test product to the reference product were 0.981 (0.943-1.020) and 0.978 (0.955-1.001) in Study I, and 0.973 (0.944-1.003) and 1.004 (0.983-1.025) in Study II, respectively. In both studies, the 90% CI values of the GLSM ratios of C and AUC were within the prespecified bioequivalence range (0.80-1.25). The safety of the test product under both dosing conditions and that of the reference product were not different.
The new dry syrup formulation containing memantine hydrochloride showed bioequivalence to the film-coated tablet under the two dosing conditions. Thus, the new dry syrup is suitable under either dosing condition for patients with AD.
Daiichi Sankyo Co., Ltd.
盐酸美金刚是一种 N-甲基-D-天冬氨酸受体拮抗剂，用于治疗阿尔茨海默病（AD）。为提高 AD 患者的用药依从性，减轻家庭和照护者负担，开发了一种新的盐酸美金刚干糖浆制剂。本研究旨在评估该新制剂与片剂的生物等效性。
进行了两项单剂量、随机、开放标签、两周期、两制剂、交叉研究，以评估在两种给药条件下，受试制剂（2%、1g[含 20mg 盐酸美金刚]干糖浆，混悬于水）与参比制剂（薄膜包衣片）的生物等效性：受试制剂以混悬液形式给药（研究 I）和以颗粒形式加水送服（研究 II）。在特定时间间隔采集血样，采用经验证的液相色谱-串联质谱法测定美金刚的血浆浓度。采用非房室分析计算美金刚的药代动力学参数。采用 C 和 AUC 至最后一个采样时间（AUC）的最大浓度（C）来评估两种制剂的生物等效性。
在研究 I 中，受试制剂相对于参比制剂的 C 和 AUC 的几何均数比值（90%置信区间[CI]）分别为 0.981（0.943-1.020）和 0.978（0.955-1.001），在研究 II 中，分别为 0.973（0.944-1.003）和 1.004（0.983-1.025）。在两项研究中，C 和 AUC 的 GLSM 比值的 90%CI 值均在预设的生物等效性范围内（0.80-1.25）。两种给药条件下，受试制剂和参比制剂的安全性均无差异。
两种给药条件下，盐酸美金刚干糖浆制剂均显示出与薄膜包衣片的生物等效性。因此，对于 AD 患者，新的干糖浆制剂无论哪种给药方式均适用。
第一三共株式会社。
