Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
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The Inhibitory Effect of Adenylic Acid on the Bitterness of the Antibacterial Combination Drug Trimethoprim/Sulfamethoxazole
Jun KawaharaMiyako YoshidaHonami KojimaRio UnoMinoru OzekiIkuo KawasakiMasaaki HabaraHidekazu IkezakiTakahiro Uchida
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2023 Volume 71 Issue 3 Pages 198-205


The purpose of the present study was to evaluate bitterness suppression effect of adenylic acid (AMP) as a nucleotide-derived nutrient enhancer on a bitter commercial drug. In the present study, we evaluated peripheral bitterness inhibition effect of AMP on the trimethoprim (TMP) and sulfamethoxazole (SMZ) combination formulation based on taste sensor. The taste sensor values of TMP solutions with different concentrations show large sensor output in correlation with the concentration of TMP, whereas no sensor output in shown for the SMZ solutions. Therefore, the bitterness of this combination formulation is mainly due to TMP. We evaluated the TMP bitterness inhibitory effects of AMP, sodium salt of AMP (AMP Na; sodium adenylate), sodium salt of GMP (GMP Na; sodium guanylate), and sodium salt of inosine monophosphate (IMP Na; sodium inosinate), and found that only AMP displayed very effective bitterness inhibition. MarvinSketch analysis revealed that potential electrostatic interaction between cationized TMP and anionized forms (II and III) of AMP may cause bitterness suppression. 1H-NMR study suggested an interaction of TMP and AMP molecules based on chemical shift perturbations and an interaction between the phosphate group of AMP and amino group of TMP. Lastly, conventional elution analysis simulating oral cavity capacity for up to one minute were performed using commercial TMP/SMZ combination granules. The sensor output gradually increased up to 60 s. The addition of AMP solution to the eluted sample at 60 s significantly decreased the bitterness sensor output of the eluted sample.

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