The aim of this study was to evaluate bitterness by using “CCDP; Change in concentration-dependent potential” considering dose-dependency of active pharmaceutical ingredients (APIs) as new and useful bitterness evaluation index compared with bitter sensor output value which is conventional bitterness evaluation index for 48 pediatric medicines from the recent edition of the WHO model list of essential medicines for children (7th edn, 2019). Solutions (0.01, 0.03, 0.1 mM) of the compounds were evaluated by an artificial taste sensor using membranes sensitive to bitterness. The dose–response slope of the sensor outputs was defined as CCDP. On the basis of principal component analysis of CCDPs, chlorpromazine hydrochloride, amitriptyline hydrochloride, propranolol hydrochloride, primaquine phosphate and haloperidol were predicted to express the strongest levels of basic bitterness, surpassing that of quinine hydrochloride. Correlation analysis (Fisher’s exact tests and multiple regression analysis) was performed to determine the relation between CCDPs and various physicochemical properties participated in hydrophilicity and hydrophobicity. It is revealed that contribution physicochemical factors are different by individual basic bitterness sensor (AC0, AN0 or BT0), and this result becomes the criterion of the sensor choice to evaluate basic bitterness intensity using basic bitterness sensors. Hydrophobic and hydrophilic interactions could be simulated by ligand docking modeling for haloperidol, miconazole and quinine hydrochloride. The pharmaceutical products need a bitterness evaluation in consideration of concentration-dependency to vary in a dose depending on a patient individual. Thus, it was concluded that CCDP correlated to hydrophilicity and hydrophobicity is useful as a bitterness evaluation index of APIs in pediatric medicines.

本研究的目的是通过使用“CCDP；将活性药物成分 (API) 的剂量依赖性作为新的和有用的苦味评价指标，与最近版 WHO 模型清单中 48 种儿科药物的传统苦味评价指标苦味传感器输出值相比，浓度依赖性潜力的变化”儿童基本药物（第 7 版，2019 年）。通过使用对苦味敏感的膜的人工味觉传感器评估化合物的溶液（0.01、0.03、0.1mM）。传感器输出的剂量响应斜率定义为 CCDP。在对CCDPs、盐酸氯丙嗪、盐酸阿米替林、盐酸普萘洛尔进行主成分分析的基础上，预计磷酸伯氨喹和氟哌啶醇会表现出最强的碱性苦味，超过盐酸奎宁。进行相关分析（Fisher 精确检验和多元回归分析）以确定 CCDP 与参与亲水性和疏水性的各种理化性质之间的关系。揭示了不同基础苦味传感器（AC0、AN0或BT0）对物理化学因素的贡献不同，该结果成为使用基础苦味传感器评估基础苦味强度的传感器选择标准。可以通过氟哌啶醇、咪康唑和盐酸奎宁的配体对接模型来模拟疏水和亲水相互作用。药物产品需要考虑到浓度依赖性以根据患者个体而改变剂量的苦味评价。因此，可以得出结论，与亲水性和疏水性相关的 CCDP 可用作儿科药物中 API 的苦味评价指标。