A Systematic Review of Gastric Acid-Reducing Agent-Mediated Drug-Drug Interactions with Orally Administered Medications.

BACKGROUND AND OBJECTIVE: Several review articles have been published discussing gastric acid-related drug-drug interactions (DDIs) mediated by coadministration of antacids, histamine H2 receptor antagonists, or proton pump inhibitors, but are not sufficiently comprehensive in capturing all documented DDIs with acid-reducing agents (ARAs) and tend to focus on gastric pH-dependent DDIs and/or basic drugs. Subsequently, several new drugs have been approved, and new information is available in the literature. The objective of this systematic review is to comprehensively identify oral medications that have clinically meaningful DDIs, including loss of efficacy or adverse effects, with gastric ARAs, and categorize these medications according to mechanism of interaction. METHODS: An indepth search of clinical data in the PDR3D: Reed Tech Navigator™ for Drug Labels, University of Washington Drug-Drug Interaction Database, DailyMed, Drugs@FDA.gov, and UpToDate®/Lexicomp® Drug and Drug Interaction screening tool was conducted from 1 June to 1 August 2018. The PDR3D, University of Washington Drug-Drug Interaction Database, and DailyMed were searched with terms associated with gastric acid and ARAs. Conflicting findings were further investigated using the UpToDate®/Lexicomp® screening tool. Clinical relevance was assessed on whether an intervention was needed, and prescribing information and/or literature supporting the DDI. RESULTS: Through the search strategy, 121 medications were found to clinically meaningfully interact with ARAs. For 38 medications the mechanism of interaction with ARAs was identified as gastric pH dependent, and for 83 medications the interaction was found to be not gastric pH mediated, with mechanisms involving metabolic enzymes, transporters, chelation, and urine alkalization. Additionally, 109 medications were studied and did not have a clinically meaningful interaction with ARAs. CONCLUSION: This review may provide a resource to healthcare professionals in aiding the care of patients by increasing awareness of interactions with ARAs and may also identify and potentially aid in avoiding clinically relevant DDIs and preventing risk of treatment failure and/or adverse effects. Advances in non-clinical predictions of gastric pH-mediated DDIs may guide the need for a future clinical evaluation.

Structural and antioxidant modification of wheat peptides modified by the heat and lipid peroxidation product malondialdehyde.

Wheat peptides, the biological active peptides derived from foods, has an array of biological actions, including antiobesity, antimicrobial, and angiotensin I-converting enzyme inhibitory effects in mammalian species. Recent studies showed that some wheat peptides may show the noteworthy antioxidant potency against the peroxidation of lipids or fatty acids, but the effect of oxidation on its antioxidant activities is unclear. In the present study, we demonstrate that heat and malandialdehyde (MDA)-oxidized wheat peptides lose its surface hydrophobicity and reducing power, and show a relatively lower free radical-scavenging activitiy in vitro. Those modifications also lead to gradual formation of aggregates in wheat peptides and induce more reactive oxygen species (ROS) production in vivo. These findings indicate that oxidation may influence the functional properties and directly alter the structure of wheat peptides, and lead to the loss of its antioxidant potency both in vitro and in vivo, thereby providing a novel explanation for some of the potential health risks proposed for oxidized food in human.

Murine local lymph node assay for predictive testing of allergenicity: two irritants caused significant proliferation.

The murine local lymph node assay is a method for predictive testing of contact allergenicity, but its ability to discriminate between allergens and irritants has been questioned. To explain some of the conflicting results with irritants, the proliferation induced by methyl salicylate and nonanoic acid, both considered to be non-sensitisers, was further investigated. Both substances showed a dose--response relationship and clearly positive results when tested at higher concentrations (> or = 50%) and would thus be classified as potential sensitisers according to the present criteria for a positive assay result. In the case of methyl salicylate, the use of either dimethyl formamide or methyl ethyl ketone as vehicle did not significantly influence the results. The negative results obtained for methyl salicylate in some earlier reports were probably due to testing at too low concentrations. The proliferation induced by irritants such as methyl salicylate and nonanoic acid and inter alia sodium dodecyl sulfate, Triton X-100, oxalic acid, chloroform/methanol (2:1) must be better recognized and elucidated before the assay can be generally accepted as a predictive test method.

Cytotoxicity of photosensitizers camphorquinone and 9-fluorenone with visible light irradiation on a human submandibular-duct cell line in vitro.

The cytotoxic effect of two types of photosensitizers (camphorquinone, CQ, a widely used aliphatic type and 9-fluorenone, 9F, an aromatic type) in the presence of 2-dimethylaminoethyl methacrylate (DM) as a reducing agent with exposure to visible light (350-550 nm) was examined in a human cell line. Cytotoxicity was evaluated in terms of the percentage of cell survival, and the production of reactive oxygen in living single cells was measured with an adherent cell analysis and sorting laser cytometer and a peroxide indicator. The amount of reactive oxygen generated in the cells irradiated in the 9F (1 mM-3 min) system was about 9-fold greater than under the same conditions in the CQ system. Similarly, the decrease in cell survival in the 9F system was about 10-fold greater than in the CQ. Both the production of reactive oxygen in the cells and the decrease in cell survival paralleled the concentration of photosensitizers and the irradiation time. Although the cell-damaging effects with the CQ system were mild, at a higher dose (10 mM) and longer irradiation time (24 min) it produced cell survival equal to that in the 9F (1 mM-3 min) system. These results suggest that in the case of irradiated photosensitizer systems, 9F was much more damaging to the cells than CQ, which damage probably occurred via free radicals involving reactive oxygen generation.