目的:某些药物的不良苦味是克服不遵守药物使用的障碍,特别是给儿童和老人的救命药物。这里,我们评估了一类新的苦味阻滞剂(噻唑烷二酮,TZDs)。
方法:在本研究中,测试了2个TZD,罗格列酮(ROSI)和一种更简单的TZD形式,使用高效甜味剂作为阳性对照(新橙皮苷二氢查尔酮,NHDC)。我们使用苦味药物富马酸替诺福韦alafenamide(TAF)测试了苦味阻断作用,治疗艾滋病毒和乙型肝炎感染,和吡喹酮(PRAZ),血吸虫病的治疗方法,通过使用2个单独的味觉小组进行味觉测试:一个普通小组(N=97,20-23年,82.5%女性,所有东欧)和一个基因信息小组(N=158,包括68对双胞胎,18-82岁,76%为女性,87%的欧洲血统)。参与者在100点广义视觉模拟量表上对溶液的苦味强度进行了评分。
结果:药物苦味的人与人之间的差异是惊人的;TAF和PRAZ对某些人来说是微弱的或不苦的,但对另一些人来说是中度到高度的苦味。两个口味小组的参与者将苦味药物TAF和PRAZ与NHDC混合后的平均苦味比单独取样时少。ROSI部分抑制了TAF和PRAZ的苦味,但是两个小组之间的有效性有所不同:在一般小组中,PRAZ而不是TAF的苦味显着降低,在遗传信息小组中,TAF而不是PRAZ的苦味显着降低。ROSI是比其他TZD更有效的阻断剂。
结论:这些结果表明,TZDs是部分有效的苦味阻滞剂,抑制疗效因药物而异,从人到人,从面板到面板,建议其他TZDs应该用更多的药物和不同的人群进行设计和测试,以确定哪些药物对谁最有效。苦味受体阻滞剂的发现可以改善药物使用的依从性。
OBJECTIVE: The bad bitter taste of some medicines is a barrier to overcoming noncompliance with medication use, especially life-saving drugs given to children and the elderly. Here, we evaluated a new class of bitter blockers (thiazolidinediones, TZDs).
METHODS: In this study, 2 TZDs were tested, rosiglitazone (ROSI) and a simpler form of TZD, using a high-potency sweetener as a positive control (neohesperidin dihydrochalcone, NHDC). We tested bitter-blocking effects using the bitter drugs tenofovir alafenamide fumarate (TAF), a treatment for HIV and hepatitis B infection, and praziquantel (PRAZ), a treatment for schistosomiasis, by conducting taste testing with 2 separate taste panels: a general panel (N = 97, 20-23 years, 82.5% female, all Eastern European) and a genetically informative panel (N = 158, including 68 twin pairs, 18-82 years, 76% female, 87% European ancestry). Participants rated the bitterness intensity of the solutions on a 100-point generalized visual analog scale.
RESULTS: Person-to-person differences in drug bitterness were striking; TAF and PRAZ were weakly or not bitter for some people but moderately to highly bitter for others. Participants in both taste panels rated the bitter drugs TAF and PRAZ as less bitter on average when mixed with NHDC than when sampled alone. ROSI partially suppressed the bitterness of TAF and PRAZ, but effectiveness differed between the 2 panels: bitterness was significantly reduced for PRAZ but not TAF in the general panel and for TAF but not PRAZ in the genetically informative panel. ROSI was a more effective blocker than the other TZD.
CONCLUSIONS: These results suggest that TZDs are partially effective bitter blockers and the suppression efficacy differs from drug to drug, from person to person, and from panel to panel, suggesting other TZDs should be designed and tested with more drugs and on diverse populations to define which ones work best with which drugs and for whom. The discovery of bitter receptor blockers can improve compliance with medication use.