Taste of medicines for children: genetic variation and medical adherence

一些孩子会喜欢某种药物的味道，并完成整个疗程，而另一些孩子则会喜欢 会强烈抵制它的味道，遭受味道调节的副作用，或者两者兼而有之。这些独特的变体支持 基于理解基因组变异的精确医学方法，使我们每个人都是独一无二的 有耐心的。影响将是显著的--当一个孩子拒绝服用单剂，更不用说整个疗程了，这 即使是最强大的药物也无法发挥作用。在临床护理中优先考虑品味评估，并 为了满足“适口性”品味评估的需求，这款续订应用程序有三个目标。具体目标1 将系统地测量训练有素的和分型的成年感官小组成员在品尝 各种儿科药物的液体制剂(类固醇、消炎药、免疫调节剂和 抗生素，包括克林霉素)和各种赋形剂。这一强有力的基于品味的评估将使 美国首次测量对药物的味觉反应的变化，并确定个人的味觉 对一种药物的反应预测对同一类别或类似辅料的其他药物的反应，以及 这些味觉反应如何与遗传变异相关。《特定目标2》将系统地衡量最初的口味 接受抗菌药物治疗的分型儿童患者对第一剂抗生素(克林霉素)的反应 急诊室皮肤软组织感染的诊断。将对所有患者进行跟踪，以确定是否 他们完成为期一周的药物治疗方案和/或经历副作用。因为特定的药物 副作用有患者特定的变异性，我们将确定孩子最初的味觉反应， 基因分型，或两者兼有，可预测后续副作用和用药依从性。具体目标3，结合 特定目标1和2的结果将决定分型成人小组的结果是否可转移到 儿科反应：专家小组是否预测了儿科患者对克林霉素初始口味的变化 并识别哪些患者(例如，特定基因的患者)可能对味道有问题。这样的数据 将帮助建立成人味觉小组，以评估儿科配方的适宜性和快速 基因分型在帮助选择儿科配方和方案中的作用。为了实现我们的目标，我们有 组建了一个多机构团队，带来了人类感知方面独特和必要的专业知识， 遗传学、生物医学信息学和/或儿科医学，以研究儿童的个性化感知 药物，我们怀疑这是理解用药依从性和临床的被低估的关键 成果，并解决被确定为研究和全球卫生优先事项的知识差距。数据 将为未来的临床试验提供工具和证据基础，以评估其他药物的味道和 治疗学。这些临床试验的结果将为使用患者的基因组信息奠定基础， 最初的味觉反应，或两者兼而有之，以量身定制药物和治疗方法，以最大限度地提高临床疗效，最大限度地减少 副作用。

Some children will like the taste of a given medicine and complete the full course of treatment, whereas others will strongly reject its taste, suffer taste-modulated side effects, or both. These distinctive variations support a precision medicine approach based on understanding variation in the genome that makes each of us a unique patient. The impact will be significant—when a child refuses to take a single dose, let alone a full course, this thwarts the benefits of even the most powerful drugs. To prioritize taste assessment in clinical care and to address the need for “palatability” taste assessments, this renewal application has three aims. Specific Aim 1 will systematically measure personal variation of trained and genotyped adult sensory panelists in the taste of a variety of liquid formulations of pediatric medicines (steroids, anti-inflammatories, immune modulators, and antibiotics, including clindamycin) and a variety of excipients. This vigorous taste-based assessment will allow us to measure for the first time variations in taste responses to drugs and to determine whether individual taste responses to one drug predict responses to other medicines in the same class or with similar excipients, and how these taste responses relate to genetic variations. Specific Aim 2 will systematically measure initial taste reactions to the first dose of an antibiotic (clindamycin) by genotyped pediatric patients who receive a diagnosis of skin and soft tissue infection in the emergency room. All patients will be followed to determine if they complete the 1-week medication regimen and/or experience side effects. Because medication-specific side effects have patient-specific variability, we will determine whether the child’s initial taste responses, genotype, or both predict subsequent side effects and medication adherence. Specific Aim 3, combining the outcomes of Specific Aims 1 and 2, will determine the transferability of results of a genotyped adult panel to pediatric responses: whether the panel predicts variation in the initial taste of clindamycin by pediatric patients and identifies which patients (e.g., those of a particular genotype) may have problems with the taste. Such data will help establish adult taste panels to evaluate suitability of pediatric formulations and the feasibility of rapid genotyping in helping select pediatric formulations and regimens. To accomplish our goals, we have assembled a multi-institutional team that brings unique and necessary expertise in human perception, genetics, biomedical informatics, and/or pediatric medicine to study personalized perception of pediatric medicines, which we suspect is the underappreciated key to understanding medication adherence and clinical outcomes and which addresses gaps in knowledge identified as research and global health priorities. The data generated will provide the tools and evidence base for future clinical trials to assess taste of other drugs and therapeutics. Results from such clinical trials will lay the foundation to use the patient’s genomic information, initial taste response, or both to tailor medicines and therapies to maximize clinical outcomes and minimize side effects.