Children’s perceptions about medicines: individual differences and taste

BMC Pediatrics

Danielle R. Reed¹  Phoebe S. Mathew¹  Kristi M. Roberts¹  Julie A. Mennella¹ 

[1] Monell Chemical Senses Center, 3500 Market Street, Philadelphia 19104-3308, PA, USA

关键词: Taste;    Medication;    Genetics;    Compliance;    Children;   

Others  :  1227572
DOI  :  10.1186/s12887-015-0447-z

 received in 2014-06-16, accepted in 2015-09-09,  发布年份 2015

【 摘 要 】

Background

Bitter 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.

Methods

We 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.

Results

Children (>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; χ ²  = 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).

Conclusions

Individual 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 Registration

Clinicaltrials.gov protocol registration system (NCT01407939). Registered 19 July 2011.

【 授权许可】

   
2015 Mennella et al.

【 参考文献 】

• [1]Ruark JL, McCullough GH, Peters RL, Moore CA. Bolus consistency and swallowing in children and adults. Dysphagia. 2002; 17(1):24-33.
• [2]Mennella JA, Spector AC, Reed DR, Coldwell SE. The bad taste of medicines: Overview of basic research on bitter taste. Clin Ther. 2013; 35:1225-1246.
• [3]Giacoia GP, Taylor-Zapata P, Zajicek A. Eunice Kennedy Shriver National Institute of Child Health and Human Development Pediatrics Formulation Initiative: Proceedings from the Second Workshop on Pediatric Formulations. Clin Ther. 2012; 34:S1-S10.
• [4]Schirm E, Tobi H, de Vries TW, Choonara I, De Jong-van den Berg LT. Lack of appropriate formulations of medicines for children in the community. Acta Paediatr. 2003; 92(12):1486-1489.
• [5]Nunn T, Williams J. Formulation of medicines for children. Br J Clin Pharmacol. 2005; 59(6):674-676.
• [6]Baguley D, Lim E, Bevan A, Pallet A, Faust SN. Prescribing for children - taste and palatability affect adherence to antibiotics: a review. Arch Dis Child. 2012; 97(3):293-297.
• [7]Dagan R, Shvartzman P, Liss Z. Variation in acceptance of common oral antibiotic suspensions. Pediatr Infect Dis J. 1994; 13(8):686-690.
• [8]Polaha J, Dalton WT, Lancaster BM. Parental report of medication acceptance among youth: implications for everyday practice. South Med J. 2008; 101(11):1106-1112.
• [9]Steele RW, Thomas MP, Bégué RE. Compliance issues related to the selection of antibiotic suspensions for children. Pediatr Infect Dis J. 2001; 20(1):1-5.
• [10]Milne CP, Bruss JB. The economics of pediatric formulation development for off-patent drugs. Clin Ther. 2008; 30:2133-2145.
• [11]Matsui D. Assessing palatability of medicines in children. Paediatr Perinat Drug Ther. 2007; 8:55-60.
• [12]Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B et al.. The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses. 2010; 35(2):157-170.
• [13]Mennella JA, Pepino MY, Reed DR. Genetic and environmental determinants of bitter perception and sweet preferences. Pediatrics. 2005; 115(2):e216-222.
• [14]Drayna D, Coon H, Kim UK et al.. Genetic analysis of a complex trait in the Utah Genetic Reference Project: a major locus for PTC taste ability on chromosome 7q and a secondary locus on chromosome 16p. Hum Genet. 2003; 112:567-572.
• [15]Mennella JA, Reed DR, Roberts KM, Mathew PS, Mansfield CJ. Age-related differences in bitter taste and efficacy of bitter blockers. PLoS One. 2014; 9(7):e103107.
• [16]Mennella JA, Pepino MY, Duke FF, Reed DR. Age modifies the genotype-phenotype relationship for the bitter receptor TAS2R38. BMC Genet. 2010; 11:60. BioMed Central Full Text
• [17]Lipchock SV, Reed DR, Mennella JA. Relationship between bitter-taste receptor genotype and solid medication formulation usage among young children: a retrospective analysis. Clin Ther. 2012; 34:728-733.
• [18]Mennella JA, Reed DR, Mathew PS, Roberts KM, Mansfield CJ. “A spoonful of sugar helps the medicine go down”: Bitter masking by sucrose among children and adults. Chem Senses. 2015; 40:17-25.
• [19]Bufe B, Breslin PA, Kuhn C, Reed DR, Tharp CD, Slack JP et al.. The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. Curr Biol. 2005; 15(4):322-327.
• [20]Kim UK, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D. Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science. 2003; 299(5610):1221-1225.
• [21]Pew Charitable Trust. Philadelphia: The State of the City, a 2014 Update. Philadelphia, PA 2014. Available at: http://www.pewtrusts.org/en/research-and-analysis/reports/2014/04/05/philadelphia-the-state-of-the-city-a-2014-update. Accessed 28 April 2015.
• [22]Thomson SA, Tuleu C, Wong IC, Keady S, Pitt KG, Sutcliffe AG. Minitablets: new modality to deliver medicines to preschool-aged children. Pediatrics. 2009; 123(2):e235-238.
• [23]Allen LVJ. Dosage form design and development. Clin Ther. 2008; 30(11):2102-2111.
• [24]EMEA/CHMP/PEG/194810/2005 (2006) Reflection paper: formulations of choice for the paediatric population. London: EMEA (2006). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003782.pdf. Accessed 28 April 2015.
• [25]Mennella JA, Finkbeiner S, Lipchock SV, Hwang LD, Reed DR. Preferences for salty and sweet tastes are elevated and related to each other during childhood. PLoS One. 2014; 9:e92201.
• [26]Mennella JA, Lukasewycz LD, Griffith JW, Beauchamp GK. Evaluation of the Monell forced-choice, paired-comparison tracking procedure for determining sweet taste preferences across the lifespan. Chem Senses. 2011; 36(4):345-355.
• [27]Czynewski DI, Runyan DR, Lopez MA, Calles NR. Teaching and maintaining pill swallowing in HIV-infected children. AIDS Read. 2000; 10:88-94.
• [28]Ghuman JK, Cataldo MD, Beck MH, Slifer KJ. Behavioral training for pill-swallowing difficulties in young children with autistic disorder. J. Child Adolesc. Psychopharmacol. 2004; 14(4):601-611.
• [29]Bartoshuk LM, Duffy VB, Reed D, Williams A. Supertasting, earaches and head injury: genetics and pathology alter our taste worlds. Neurosci Biobehav Rev. 1996; 79:87.
• [30]Bell KI, Tepper BJ. Short-term vegetable intake by young children classified by 6-n-propylthoiuracil bitter-taste phenotype. Am J Clin Nutr. 2006; 84(1):245-251.
• [31]Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS. A novel family of mammalian taste receptors. Cell. 2000; 100(6):693-702.
• [32]Rakhmanina NY, van den Anker JN. Pharmacological research in pediatrics: From neonates to adolescents. Adv Drug Deliv Rev. 2006; 58(1):4-14.
• [33]Liem DG, Zandstra L, Thomas A. Prediction of children's flavour preferences. Effect of age and stability in reported preferences. Appetite. 2010; 55(1):69-75.
• [34]Standing JF, Khaki ZF, Wong IC. Poor formulation information in published pediatric drug trials. Pediatrics. 2005; 116(4):e559-562.