Taste of medicines for children: genetic variation and medical adherence

儿童药物的味道：遗传变异和医疗依从性

• 批准号: 10395465
• 负责人: Elizabeth Dawn Lowenthal
• 金额: $ 40.77万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10395465
• 关键词: Accident and Emergency department; Address; Adherence; Adult; Anti-Inflammatory Agents; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Bacterial Infections; Cessation of life; Child; Childhood; Clindamycin; Clinical; Clinical Trials; Clip; Code; Data; Diagnosis; Disease; Dose; Eczema; Effectiveness; Excipients; Exhibits; Formulation; Foundations; Future; Genes; Genetic; Genetic Variation; Genome; Genomics; Genotype; Goals; Health Care Costs; Health Priorities; Human; Immunomodulators; Individual; Individual Differences; Informatics; Interview; Knowledge; Lead; Life; Liquid substance; Measures; Medical; Medical Records; Medicine; Methodology; Methods; Mothers; Nose; Oral; Outcome; Palate; Patients; Perception; Pharmaceutical Preparations; Phenotype; Play; Population; Psychophysics; Reaction; Records; Regimen; Reporting; Reproducibility; Research; Research Priority; Risk; Role; Sensory; Site; Skin Tissue; Soft Tissue Infections; Source; Steroids; Taste Buds; Taste Perception; Testing; Therapeutic; Time; Training; Variant; Videotape; base; biomedical informatics; clinical care; diaries; drug response prediction; evidence base; experience; experimental study; follow-up; genetic association; genetic variant; global health; health organization; hedonic; individual patient; individual variation; liquid formulation; medication compliance; medication nonadherence; orofacial; pediatric human immunodeficiency virus; pediatric patients; personalized medicine; precision medicine; predictive panel; response; screening; side effect; skills; tool

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.

有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这种药物。 会强烈排斥它的味道，或遭受味道调节的副作用，或两者兼而有之。这些独特的变化支持一个 精确医学方法基于对基因组变异的理解，这使得我们每个人都是独一无二的。 病人影响将是巨大的--当孩子拒绝服用一剂，更不用说服用整个疗程时，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味觉评估， 为了满足“适口性”味道评估的需要，这次更新申请有三个目的。具体目标1 将系统地测量受过训练的和基因分型的成人感官小组成员在品尝 各种儿科药物的液体制剂（类固醇、抗炎药、免疫调节剂， 抗生素，包括克林霉素）和各种赋形剂。这种基于口味的有力评估将允许 我们第一次测量对药物的味觉反应的变化，并确定个体的味觉是否 对一种药物的反应可预测对同类或含相似辅料的其他药物的反应，以及 这些味觉反应与基因变异的关系具体目标2将系统地测量初始味道 接受抗生素（克林霉素）治疗的基因型儿科患者对第一剂抗生素（克林霉素）的反应 在急诊室诊断皮肤和软组织感染。将对所有患者进行随访，以确定 他们完成1周的药物治疗方案和/或经历副作用。因为药物特异性 副作用有患者特异性的变异性，我们将确定儿童的最初味觉反应， 基因型，或两者预测随后的副作用和药物依从性。具体目标3，结合 特定目的1和2的结果，将决定基因分型成人组结果的可转移性， 儿科反应：小组是否预测儿科患者克林霉素初始味道的变化 并识别哪些患者（例如，特定基因型的那些）可能在味道上有问题。这样的数据 将有助于建立成人口味小组，以评估儿科制剂的适用性和快速 基因分型有助于选择儿科制剂和治疗方案。为了实现我们的目标，我们 组建了一个多机构团队，带来了人类感知方面独特而必要的专业知识， 遗传学、生物医学信息学和/或儿科医学，以研究儿科疾病的个性化感知。 药物，我们怀疑这是理解药物依从性和临床 该战略旨在解决被确定为研究和全球卫生优先事项的知识差距。数据 所产生的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， 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，以定制药物和疗法，以最大限度地提高临床效果，并最大限度地减少 副作用.