Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Naples, Italy.
Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy.
Biomed Pharmacother. 2021 May;137:111385. doi: 10.1016/j.biopha.2021.111385. Epub 2021 Feb 27.
A large body of evidence suggests that supplementation of butyric acid exerts beneficial intestinal and extra-intestinal effects. Unfortunately, unpleasant sensorial properties and unfavourable physico-chemical properties strongly limit its use in food supplements and foods for medicinal purposes. N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) is a new butyric acid releaser in solid form with neutral sensorial properties. The aim of this investigation is to provide preliminary information on its pharmacokinetic and toxicological properties through the study of a) in vivo bioavailability of FBA administered by oral gavage to male and female Swiss CD1 mice in comparison with sodium butyrate, b) the influence of digestion on FBA stability through an in vitro simulated oro-gastro-duodenal digestion process, and c) in vitro toxicological profile by means of the Ames Test and Micronucleus Test. The results reveal that FBA is a good butyric acid releaser, being able to increase butyrate serum concentration in a dose and time dependent manner in both male and female mice with a pharmacokinetic profile similar to that obtained from sodium butyrate as such. These data are confirmed by investigating the influence of digestion on FBA, which undergoes extensive hydrolysis following oro-gastro-duodenal digestion, especially in duodenal conditions, with a residual concentration of less than 10% of the initial FBA concentration. Finally, in the Ames and Micronucleus Tests, FBA does not show any in vitro genotoxicity as it is non mutagenic in the Ames Test and results to be unable to induce chromosome breaks in the Micronucleus Test. In conclusion, FBA is a new butyric acid releaser that can overcome the disadvantages of butyric acid while maintaining the same pharmacokinetic properties and safety profile, as shown by the results of the preliminary in vitro toxicological studies performed in this investigation.
大量证据表明，丁酸的补充对肠道和肠道外都有有益的作用。不幸的是，丁酸令人不快的感官特性和不理想的物理化学特性严重限制了它在食品补充剂和药用食品中的应用。N-(1-氨基甲酰基-2-苯基-乙基)丁酰胺（FBA）是一种新型的固体丁酸释放剂，具有中性的感官特性。本研究的目的是通过研究 a）FBA 经口服灌胃给予雄性和雌性瑞士 CD1 小鼠的体内生物利用度与丁酸钠的比较，b）通过体外模拟口腔-胃-十二指肠消化过程研究消化对 FBA 稳定性的影响，以及 c）通过 Ames 试验和微核试验进行体外毒理学研究，提供其药代动力学和毒理学特性的初步信息。结果表明，FBA 是一种良好的丁酸释放剂，能够以剂量和时间依赖的方式增加雄性和雌性小鼠的血清丁酸浓度，其药代动力学特征与丁酸钠相似。这些数据通过研究消化对 FBA 的影响得到了证实，FBA 在口腔-胃-十二指肠消化后会发生广泛水解，尤其是在十二指肠条件下，残留浓度低于初始 FBA 浓度的 10%。最后，在 Ames 试验和微核试验中，FBA 没有显示出任何体外遗传毒性，因为它在 Ames 试验中没有致突变性，并且在微核试验中不能诱导染色体断裂。总之，FBA 是一种新型的丁酸释放剂，它可以克服丁酸的缺点，同时保持相同的药代动力学特性和安全性，正如本研究中进行的初步体外毒理学研究结果所示。
