Use of Adult Sensory Panel to Study Individual Differences in the Palatability of a Pediatric HIV Treatment Drug

Abstract

Purpose The recommended first-line treatment for young children infected with human immunodeficiency virus (HIV) includes the liquid formulation of the co-formulated protease inhibitors lopinavir/ritonavir (Kaletra™). Clinical reports indicate that some children readily accept the taste of Kaletra, whereas others strongly reject it, which can deter therapeutic adherence and outcomes. Methods As a proof-of-concept approach, we used a sensory panel of genotyped adults to document the range of individual differences in the taste and palatability (hedonics) of the liquid formulation of Kaletra and other taste stimuli, including common excipients. Panelists rated taste sensations using generalized labelled magnitude scales to determine genotype-phenotype relationships. Several months later, they were retested to assess response reliability. Findings Not all panelists had the same sensory experience when tasting Kaletra. Palatability ratings varied widely, from moderate like to strongest imaginable dislike, and were reliable over time. The more irritating and bitter Kaletra tasted, the more disliked by the panelist. The more they disliked the taste of Kaletra, the more they disliked the taste of its excipient ethanol and the bitter stimulus denatonium. Those who experienced less bitter and sweeter taste sensations had a different genetic signature than the others. Bitterness and irritation ratings of Kaletra varied by the orphaned bitter receptor gene, TAS2R60, whereas sweetness ratings of Kaletra varied by the cold receptor gene, TRPM8 which is activated by menthol, an excipient of Kaletra. Neither genotype related to ratings for ethanol or denatonium, however. Implications The use of a sensory panel holds promise as a first step in determining the nature of individual differences in the palatability of existing pediatric drug formulations and sources of variation. In this era of personalized medicine, the need is great to develop psychophysical tools to determine which drugs will show variation in acceptance by children and whether patterns of individual variation in taste as assessed by adults mirror those of young patients.

Time to treatment disruption in children with HIV-1 randomized to initial antiretroviral therapy with protease inhibitors versus non-nucleoside reverse transcriptase inhibitors

“…Pediatric granules, especially in the four-in-one combination, may improve palatability and decrease pill burden [ 35 , 64 ]. Precision medicine related to taste-sensing genotypes may hold promise for prescribing according to individualized palatability [ 65 ]. In adult data, integrase strand transferase inhibitors (INSTIs) have been at least as tolerable as PIs or NNRTIs, if not more so, and INSTIs are increasingly preferred drugs in children [ 66 – 69 ].…”

“…Pediatric granules, especially in the four-in-one combination, may improve palatability and decrease pill burden [35,64]. Precision medicine related to taste-sensing genotypes may hold promise for prescribing according to individualized palatability [65].…”

Bitter-blockers as a taste masking strategy: A systematic review towards their utility in pharmaceuticals

“…Not everyone perceives medicines the same way; nuisances in genetic makeup play a role in the palatability of drugs [16]. TAS2Rs have extensive diversity across human populations around the world [17].…”

Development of Innovative Polymer-Based Matricial Nanostructures for Ritonavir Oral Administration

“…This was made explicit in the small taste variations shown between NP R -900 and the RIT solution. Other limitations are the individual genetic differences between the individuals and that the volunteers do not have the same sensory experience as children tasting the liquid formulation [36].…”