METHODS: As a proof-of-concept approach, a sensory panel of genotyped adults was used to document the range of individual differences in the taste and palatability (hedonics) of the liquid formulation of Kaletra and other taste stimuli, including common excipients. Panelists rated taste sensations using generalized labeled magnitude scales to determine genotype-phenotype relationships. Several months later, the panelists were retested to assess response reliability.
RESULTS: Not all panelists had the same sensory experience when tasting Kaletra. Palatability ratings varied widely, from moderate like to strongest imaginable dislike, and were reliable over time. The more irritating and bitter Kaletra tasted, the more disliked by the panelist. The more they disliked the taste of Kaletra, the more they disliked the taste of its excipient ethanol and the bitter stimulus denatonium. Those who experienced less bitter and sweeter taste sensations had a different genetic signature than the other panelists. Bitterness and irritation ratings of Kaletra varied by the orphaned bitter receptor gene (TAS2R60), whereas sweetness ratings of Kaletra varied according to the cold receptor gene (TRPM8), which is activated by menthol, an excipient of Kaletra. Neither genotype related to ratings for ethanol or denatonium, however.
CONCLUSIONS: The use of a sensory panel holds promise as a first step in determining the nature of individual differences in the palatability of existing pediatric drug formulations and sources of variation. In this era of personalized medicine, the need is great to develop psychophysical tools to determine which drugs will show variation in acceptance by children and whether patterns of individual variation in taste as assessed by adults mirror those of young patients. ClinicalTrials.gov identifier: NCT01841710.
方法:作为概念验证方法,使用基因型成人的感官小组来记录Kaletra和其他味道刺激物的液体制剂的味道和适口性(享乐学)的个体差异范围,包括常见的赋形剂。小组成员使用广义标记的幅度量表对味觉进行评级,以确定基因型-表型关系。几个月后,对小组成员进行了重新测试,以评估应答可靠性.
结果:并非所有小组成员在品尝Kaletra时都具有相同的感官体验。适口性评级差异很大,从适度的喜欢到最强烈的可以想象的厌恶,并且随着时间的推移是可靠的。卡莱特拉尝起来越刺激越苦涩,更不喜欢的小组成员。他们越不喜欢卡莱特拉的味道,他们越不喜欢其赋形剂乙醇的味道和苦味刺激detanonium。那些经历较少的苦味和甜味觉的人与其他小组成员相比具有不同的遗传特征。Kaletra的苦味和刺激性等级因孤儿苦味受体基因(TAS2R60)而异,而Kaletra的甜度等级根据冷受体基因(TRPM8)而变化,它被薄荷醇激活,Kaletra的赋形剂。基因型与乙醇或变性鎓的评级都不相关,however.
结论:感官小组的使用有望作为确定现有儿科药物配方适口性个体差异和变异来源的第一步。在这个个性化医疗的时代,需要开发心理物理学工具,以确定哪些药物会在儿童接受方面表现出差异,以及成年人评估的个体味觉变化模式是否与年轻患者相同。ClinicalTrials.gov标识符:NCT01841710。