Sweeteners are often added to liquid formulations of drugs but whether they merely make them better tasting or actually reduce the perception of bitterness remains unknown. In a group of children and adults, we determined whether adding sucrose to urea, caffeine, denatonium benzoate, propylthiouracil (PROP), and quinine would reduce their bitterness using a forced-choice method of paired comparisons. To better understand individual differences, adults also rated each solution using a more complex test (general Labeled Magnitude Scale [gLMS]) and were genotyped for the sweet taste receptor gene TAS1R3 and the bitter receptor TAS2R38. Sucrose suppressed the bitterness of each agent in children and adults. In adults, sucrose was effective in reducing the bitterness ratings from moderate to weak for all compounds tested, but those with the sensitive form of the sweet receptor reported greater reduction for caffeine and quinine. For PROP, sucrose was most effective for those who were genetically the most sensitive, although this did not attain statistical significance. Not only is the paired comparison method a valid tool to study how sucrose improves the taste of pediatric medicines among children but knowledge gleaned from basic research in bitter taste and how to alleviate it remains an important public health priority.

BackgroundBitter taste is the primary culprit for rejection of pediatric liquid medications. We probed the underlying biology of bitter sensing and the efficacy of two known bitter blockers in children and adults.MethodsA racially diverse group of 154 children (3-10 years old) and their mothers (N = 118) evaluated the effectiveness of two bitter blockers, sodium gluconate (NaG) and monosodium glutamate (MSG), for five food-grade bitter compounds (quinine, denatonium benzoate, caffeine, propylthiouracil (PROP), urea) using a forced-choice method of paired comparisons. The trial was registered at clinicaltrials.gov (NCT01407939).ResultsThe blockers reduced bitterness in 7 of 10 bitter-blocker combinations for adults but only 3 of 10 for children, suggesting that efficacy depends on age and is also specific to each bitter-blocker combination. Only the bitterness of urea was reduced by both blockers in both age groups, whereas the bitterness of PROP was not reduced by either blocker in either age group regardless of TAS2R38 genotype. Children liked the salty taste of the blocker NaG more than did adults, but both groups liked the savory taste of MSG equally.Conclusions and RelevanceBitter blocking was less effective in children, and the efficacy of blocking was both age and compound specific. This knowledge will pave the way for evidence-based strategies to help develop better-tasting medicines and highlights the conclusion that adult panelists and genotyping alone may not always be appropriate in evaluating the taste of a drug geared for children.

BackgroundBitter taste receptors are genetically diverse, so children likely vary in sensitivity to the “bad” taste of some pediatric formulations. Based on prior results that variation in a bitter taste receptor gene, TAS2R38, was related to solid (pill) formulation usage, we investigated whether this variation related to liquid formulation usage and young children’s reports of past experiences with medicines and whether maternal reports of these past experiences were concordant with those of their children.MethodsWe conducted retrospective interviews of 172 children 3 to 10 years old and their mothers (N = 130) separately in a clinical research setting about issues related to medication usage. Children were genotyped for the TASR38 variant A49P (alanine to proline at position 49). Children’s responses were compared with their TAS2R38 genotype and with maternal reports.ResultsChildren (>4 years) reported rejecting medication primarily because of taste complaints, and those with at least one sensitive TAS2R38 allele (AP or PP genotype) were more likely to report rejecting liquid medications than were those without a taster allele (AA genotype; χ2 = 5.72, df = 1, p = 0.02). Children’s and mothers’ reports of the children’s past problems with medication were in concordance (p = 0.03).ConclusionsIndividual differences in taste responses to medications highlight the need to consider children’s genetic variation and their own perceptions when developing formulations acceptable to the pediatric palate. Pediatric trials could systematically collect valid information directly from children and from their caregivers regarding palatability (rejection) issues, providing data to develop well-accepted pediatric formulations that effectively treat illnesses for all children.Trial RegistrationClinicaltrials.gov protocol registration system (NCT01407939). Registered 19 July 2011.