The Relationship between Bitter Taste Sensor Response and Physicochemical Properties of 47 Pediatric Medicines and Their Biopharmaceutics Classification
The Relationship between Bitter Taste Sensor Response and Physicochemical Properties of 47 Pediatric Medicines and Their Biopharmaceutics Classification
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DOI：
10.1248/cpb.c19-00508
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发表时间：
2019-12-01
影响因子：
1.7
通讯作者：
Uchida, Takahiro
中科院分区：
文献类型：
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作者：
Haraguchi, Tamami;Okuno, Takayoshi;Uchida, Takahiro
本研究的目的是调查47种儿科药物对苦味味觉传感器的响应与理化参数之间的关系，并根据生物药剂学分类系统（BCS）对这些药物进行分类。研究中使用了47种苦味化合物，其中大多数位于世界卫生组织2017年3月的儿童基本药物标准清单上。使用对苦味敏感的膜，通过人工味觉传感器对（0.1 mM的）溶液进行评估。基于味觉传感器测量值的主成分分析，预计氯丙嗪、氟哌啶醇、普萘洛尔、阿米替林、苯海拉明表现出最强的碱性苦味水平，超过奎宁。然后进行了苦味味觉传感器输出与理化性质之间的相关性测试，并根据其生物药剂学性质对化合物进行了分类。高log P值（≥2.82）、生理电荷（≥1）、低log S值（< - 4.5）以及高熔点（≥150°C）与苦味味觉传感器的响应呈正相关（p < 0.05）。根据BCS分类，大多数化合物被归类为第2类（低溶解性 - 高渗透性），少数为第1类（高溶解性 - 高渗透性）和第4类（低溶解性 - 低渗透性）。这些结果表明，苦味味觉传感器可用于预测儿科药物的苦味强度，并可能有助于根据其生物药剂学性质对药物进行分类。
The purpose of this study was to investigate the relationship between response to the bitterness taste sensor and physicochemical parameters of 47 pediatric medicines and to classify these medicines according to the biopharmaceutics classification system (BCS). Forty-seven bitter compounds, most of which were on the WHO model list of essential medicines for children (March 2017), were used in the study. Solutions (0.1 mM) were evaluated by an artificial taste sensor using membranes sensitive to bitterness. On the basis of principal component analysis of taste sensor measurements, chlorpromazine, haloperidol, propranolol, amitriptyline, diphenhydramine were predicted to express the strongest levels of basic bitterness, surpassing that of quinine. Correlation tests between bitter taste sensor outputs and physicochemical properties were then carried out and the compounds classified in terms of their biopharmaceutical properties. High log P values (>= 2.82), physiological charge (>= 1), low log S values (