Ruiz Fabrice, Keeley Alexander, Léglise Patrick, Tuleu Catherine, Lachuer Célia, Rwabihama Jean-Paul, Bachalat Nathalie, Boulaich Imad, Abdallah Fattima, Rabus Maité, Ribemont Annie-Claude, Michelon Hugues, Wojcicki Amélie Dufaÿ, Orlu Mine, Vallet Thibault, Boudy Vincent
ClinSearch, 110 Avenue Pierre Brossolette, 92240 Malakoff, France.
Department of Pharmaceutics, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK.
Pharmaceutics. 2019 Aug 1;11(8):368. doi: 10.3390/pharmaceutics11080368.
Palatability is a recognized driver of medicine acceptability in pediatrics but deemed less relevant in older populations due to sensory decline. Preliminary findings from an observational study implicated palatability problems with one Alzheimer's medicine. Among 1517 observer reports combining multiple measures on medicines uses in patients aged over 64, we focused on two original formulations of memantine (Ebixa, tablets ( = 25) and oral solution ( = 60)). Evaluations were scored with an acceptability reference framework (CAST), the rodent Brief Access Taste Aversion (BATA) model tested aversiveness. Focusing on women treated with Ebixa ( = 54), the oral formulation sub-group was classified as "negatively accepted", while the coated tablet was associated with the "positively accepted" cluster. In men, both formulations belonged to the "positively accepted" profile. Using BATA, the original oral solution was categorized as highly aversive/untolerated while solutions of excipients only were well tolerated. Furthermore, the number of licks was significantly lower in female than in male rats. These results revealed that medicine palatability remains important for acceptability in older populations. Moreover, converging results from humans and animal models highlighted that palatability profiles can significantly vary between the sexes. These drivers should be closely considered during drug development to enhance acceptability in this population.
适口性是儿科药物可接受性的一个公认驱动因素，但由于感官功能下降，在老年人群中被认为相关性较低。一项观察性研究的初步结果表明，一种治疗阿尔茨海默病的药物存在适口性问题。在1517份关于64岁以上患者用药多种指标的观察报告中，我们重点关注了两种美金刚的原始剂型（易倍申，片剂（n = 25）和口服溶液（n = 60））。评估采用可接受性参考框架（CAST）进行评分，啮齿动物简易味觉厌恶（BATA）模型测试厌恶程度。以服用易倍申的女性（n = 54）为重点，口服剂型亚组被归类为“负面接受”，而包衣片与“正面接受”组相关。在男性中，两种剂型都属于“正面接受”类型。使用BATA模型，原始口服溶液被归类为高度厌恶/无法耐受，而仅含辅料的溶液耐受性良好。此外雌性大鼠的舔舐次数明显低于雄性大鼠。这些结果表明，药物适口性对老年人群的可接受性仍然很重要。此外，来自人类和动物模型的趋同结果突出表明，适口性特征在性别之间可能存在显著差异。在药物研发过程中应密切考虑这些驱动因素，以提高该人群对药物的可接受性。
