The mechanisms of pharmacokinetic food-drug interactions - A perspective from the UNGAP group

The simultaneous intake of food and drugs can have a strong impact on drug release, absorption, distribution, metabolism and/or elimination and consequently, on the efficacy and safety of pharmacotherapy. As such, food-drug interactions are one of the main challenges in oral drug administration. Whereas pharmacokinetic (PK) food-drug interactions can have a variety of causes, pharmacodynamic (PD) food-drug interactions occur due to specific pharmacological interactions between a drug and particular drinks or food. In recent years, extensive efforts were made to elucidate the mechanisms that drive pharmacokinetic food-drug interactions. Their occurrence depends mainly on the properties of the drug substance, the formulation and a multitude of physiological factors. Every intake of food or drink changes the physiological conditions in the human gastrointestinal tract. Therefore, a precise understanding of how different foods and drinks affect the processes of drug absorption, distribution, metabolism and/or elimination as well as formulation performance is important in order to be able to predict and avoid such interactions. Furthermore, it must be considered that beverages such as milk, grapefruit juice and alcohol can also lead to specific food-drug interactions. In this regard, the growing use of food supplements and functional food requires urgent attention in oral pharmacotherapy. Recently, a new consortium in Understanding Gastrointestinal Absorption-related Processes (UNGAP) was established through COST, a funding organisation of the European Union supporting translational research across Europe. In this review of the UNGAP Working group "Food-Drug Interface", the different mechanisms that can lead to pharmacokinetic food-drug interactions are discussed and summarised from different expert perspectives

Corrigendum to "European contribution to the study of ROS:A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)" [Redox Biol. 13 (2017) 94-162]

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed

Current challenges and future perspectives in oral absorption research: An opinion of the UNGAP network

Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists on four key themes across the oral absorption landscape: (1) specific patient populations, (2) regional differences in the gastrointestinal tract, (3) advanced formulations and (4) food-drug interactions. The differences of oral absorption in pediatric and geriatric populations, the specific issues in colonic absorption, the formulation approaches for poorly water-soluble (small molecules) and poorly permeable (peptides, RNA etc.) drugs, as well as the vast realm of food effects, are some of the topics discussed in detail. The identified controversies and gaps in the current understanding of gastrointestinal absorption-related processes are used to create a roadmap for the future of oral drug absorption research

Phenolic acid contents of kale (Brassica oleraceae L. var. acephala DC.) extracts and their antioxidant and antibacterial activities

Nine phenolic acids were identified and quantified by HPLC-MS in leaves and 10 in seeds of kale (black cabbage). The free, ester (methanol-soluble), glycoside and ester-bound (methanol-insoluble) phenolic acid contents of the leaves were 487, 532, 4989 and 6402 ng/g fresh weight, respectively. Ferulic and caffeic acids (total contents; 4269 and 4887 ng/g, respectively) were the most abundant. The seed contents of these fractions were 1993, 1477, 1231 and 4909 ng/g dry weight (DW), respectively, and sinapic acid was the most abundant (5037 ng/g DW). The fractions' total phenolic contents, determined colorimetrically, were highly correlated with their DPPH scavenging capacity, and in antimicrobial activity assays, with nine test organisms representing a wide array of taxa, all of the fractions were effective against Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis and (most strongly) Moraxella catarrhalis. Antimicrobial and antioxidant activities of kale phenolics in free and conjugated forms are discussed. © 2007 Elsevier Ltd. All rights reserved.MSM 6198959216 Karadeniz Teknik Üniversitesi: TBAG 2341, 103T152, 2004.111.004.6This work was supported by the Czech Ministry of Education (MSM 6198959216). Some of the chemicals and reagents used in the present study were purchased using funds awarded by the Research Fund of Karadeniz Technical University (Project No.: 2004.111.004.6) and Tübitak (Project No.: TBAG 2341 (103T152). We wish to thank Sees-editing Ltd. for language editing

Enzymatic oxidative dimerization of silymarin flavonolignans

Dimerization of phenolic compounds can potentially enhance their biological (antioxidant) activity. We present here the selective oxidative dimerization of several flavonolignans from Silybum marianum seed extract, namely, silybin A (1a), silybin B (1b), silychristin (3), and silydianin (4) catalyzed by a laccase from Trametes versicolor. Selective benzylation of C-7 OH group of both silybins ensured the priority of the dimerization reaction, avoiding thus polymerization. C C homodimers connected via E-rings of silybin A and B and silydianin dimers were successfully isolated after respective debenzylation. On the contrary, dimerization of 7-O-benzyl silychristin afforded a complex, inseparable mixture ofthe products. All isolated flavonolignan dimers exhibited significantly improved 1,1-diphenyl-2-picrylhydrazyl(DPPH) radical scavenging activity compared to their monomers and, therefore, seem to be promising for further biological studies.This work was supported a bilateral Czech-Italian inter-academic project IT 2012/02 between CNR and AVČR (2013-2015, V.K. + S.R.) and by COST Chemistry CM1303 Action. E.V. acknowledges support from Czech Science Foundation Grant 14-14373P and V.K. acknowledges MSMT Grant LD13041 and research concept of the Institute of MicrobiologyRVO61388971. S.R. acknowledges support from MIUR, Italy, Progetto PRIN 2011 “PROxi”