In Silico Food-Drug Interaction: A Case Study of Eluxadoline and Fatty Meal

A. Maruca, A. Lupia, R. Rocca*, D. Keszthelyi, M. Corsetti, S. Alcaro

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Food-drug interaction is an infrequently considered aspect in clinical practice. Usually, drugs are taken together with meals and what follows may adversely affect pharmacokinetic and pharmacodynamic properties, and hence, the therapeutic effects. In this study, a computational protocol was proposed to explain the different assimilations of two µ-receptors agonists, eluxadoline and loperamide, with a peculiar pharmacokinetic profile. Compared to loperamide, eluxadoline is absorbed less after the intake of a fatty meal, and the LogP values do not explain this event. Firstly, keeping in mind the different pH in the intestinal tract, the protonation states of both compounds were calculated. Then, all structures were subjected to a conformational search by using MonteCarlo and Molecular Dynamics methods, with solvation terms mimicking the water and weak polar solvent (octanol). Both computational results showed that eluxadoline has less conformational freedom in octanol, unlike loperamide, which exhibits constant behavior in both solvents. Therefore, we hypothesize that fatty meal causes the “closure” of the eluxadoline molecule to prevent the exposure of the polar groups and their interaction with water, necessary for the drug absorption. Based on our results, this work could be a reasonable “case study”, useful for future investigation of the drug pharmacokinetic profile.

Original languageEnglish
Article number9127
Number of pages16
JournalInternational Journal of Molecular Sciences
Issue number23
Publication statusPublished - 1 Dec 2020


  • conformational analysis
  • eluxadoline
  • food-drugs interactions
  • loperamide
  • molecular dynamics
  • 1ST
  • IBS

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