Taste of medicines for children: genetic variation and medical adherence

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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.