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Clinical Therapeutics Apr 2021Tegoprazan is a potassium-competitive acid blocker used for gastric acid suppression, which may be used with Helicobacter pylori eradication therapies. The goal of this...
PURPOSE
Tegoprazan is a potassium-competitive acid blocker used for gastric acid suppression, which may be used with Helicobacter pylori eradication therapies. The goal of this study was to evaluate the pharmacokinetic interaction between tegoprazan and triple-antibiotic therapy containing metronidazole, tetracycline, and bismuth.
METHODS
An open-label, 2-cohort, randomized, multiple-dose, crossover study was conducted in healthy subjects. In cohort 1, tegoprazan (100 mg/d) was administered orally with or without triple-antibiotic therapy (1500 mg/d metronidazole, 2000 mg/d tetracycline, and 1200 mg/d bismuth) for 7 days in each period. In cohort 2, triple-antibiotic therapy was administered orally with or without tegoprazan for 7 days in each period. Pharmacokinetic blood samples were collected within 24 h after the last dose. Safety assessments were performed.
FINDINGS
Eleven cohort 1 subjects and ten cohort 2 subjects were included in the pharmacokinetic analysis. The AUC and C at steady state geometric mean ratios (90% CIs) were 0.78 (0.73-0.83) and 0.75 (0.68-0.82) for tegoprazan; 0.77 (0.68-0.88) and 0.84 (0.72-0.98) for tegoprazan metabolite M1; 1.03 (0.98-1.08) and 1.08 (0.99-1.18) for metronidazole; 0.63 (0.56-0.70) and 0.64 (0.56-0.74) for tetracycline; and 1.55 (0.99-2.44) and 1.38 (0.72-2.66) for bismuth, respectively. All reported adverse events were mild.
IMPLICATIONS
Changes in the tegoprazan, tetracycline, and bismuth pharmacokinetic parameters were detected after concurrent administration. These changes were considered mainly due to the pharmacodynamic effect of tegoprazan. The adverse events were predictable and reported as frequent adverse events during triple-antibiotic therapy. There were no significant differences in safety or tolerability between quadruple therapy, including tegoprazan and triple-antibiotic therapy. ClinicalTrials.gov identifier: NCT04066257.
Topics: Anti-Bacterial Agents; Benzene Derivatives; Bismuth; Cross-Over Studies; Drug Therapy, Combination; Healthy Volunteers; Helicobacter Infections; Helicobacter pylori; Humans; Imidazoles; Male; Metronidazole; Republic of Korea; Tetracycline
PubMed: 33637332
DOI: 10.1016/j.clinthera.2021.01.026 -
International Journal of Nanomedicine 2023is an infectious pathogen and the leading cause of gastrointestinal diseases, including gastric adenocarcinoma. Currently, bismuth quadruple therapy is the recommended... (Review)
Review
is an infectious pathogen and the leading cause of gastrointestinal diseases, including gastric adenocarcinoma. Currently, bismuth quadruple therapy is the recommended first-line treatment, and it is reported to be highly effective, with >90% eradication rates on a consistent basis. However, the overuse of antibiotics causes to become increasingly resistant to antibiotics, making its eradication unlikely in the foreseeable future. Besides, the effect of antibiotic treatments on the gut microbiota also needs to be considered. Therefore, effective, selective, antibiotic-free antibacterial strategies are urgently required. Due to their unique physiochemical properties, such as the release of metal ions, the generation of reactive oxygen species, and photothermal/photodynamic effects, metal-based nanoparticles have attracted a great deal of interest. In this article, we review recent advances in the design, antimicrobial mechanisms and applications of metal-based nanoparticles for the eradication of . Additionally, we discuss current challenges in this field and future perspectives that may be used in anti- strategies.
Topics: Humans; Helicobacter Infections; Helicobacter pylori; Proton Pump Inhibitors; Drug Therapy, Combination; Anti-Bacterial Agents; Bismuth; Nanoparticles
PubMed: 37192898
DOI: 10.2147/IJN.S405052 -
Gut and Liver Jan 2022The treatment of refractory remains challenging in clinical practice. Factors that should be considered in the treatment of refractory infection include treatment... (Review)
Review
The treatment of refractory remains challenging in clinical practice. Factors that should be considered in the treatment of refractory infection include treatment length, dosage of antibiotics and proton pump inhibitors (PPIs), number of drugs, and the selection of appropriate antibiotics. Extending the treatment length of triple therapy and non-bismuth quadruple therapy to 14 days may increase the eradication rate compared with a shorter period (7 or 10 days). The use of a higher dose of PPIs or vonoprazan may also increase the efficacy of triple therapy. Four-drug therapy, including bismuth or non-bismuth quadruple therapies, usually achieve higher eradication rates than triple therapy. The addition of bismuth or metronidazole to levofloxacin-amoxicillin-PPI therapy may also increase the eradication rate. Therefore, four-drug therapies containing a higher dose of PPIs for 14 days are recommended in the third-line treatment setting for refractory infection. The selection of appropriate antibiotics may be guided by susceptibility testing or empirically by medication history. Tailored therapy guided by susceptibility testing or genotypic resistance is recommended whenever possible. However, properly designed empirical therapy based on prior medication history (i.e., avoid the reuse of clarithromycin or levofloxacin empirically) is an acceptable alternative to tailored therapy after considering accessibility, cost, and the preference of the patient.
Topics: Amoxicillin; Anti-Bacterial Agents; Bismuth; Clarithromycin; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Metronidazole; Proton Pump Inhibitors
PubMed: 33782215
DOI: 10.5009/gnl20330 -
Molecules (Basel, Switzerland) Aug 2023Bismuth-based drugs have been used primarily to treat ulcers caused by and other gastrointestinal ailments. Combined with antibiotics, these drugs also possess... (Review)
Review
Bismuth-based drugs have been used primarily to treat ulcers caused by and other gastrointestinal ailments. Combined with antibiotics, these drugs also possess synergistic activity, making them ideal for multiple therapy regimens and overcoming bacterial resistance. Compounds based on bismuth have a low cost, are safe for human use, and some of them are also effective against tumoral cells, leishmaniasis, fungi, and viruses. However, these compounds have limited bioavailability in physiological environments. As a result, there is a growing interest in developing new bismuth compounds and approaches to overcome this challenge. Considering the beneficial properties of bismuth and the importance of discovering new drugs, this review focused on the last decade's updates involving bismuth compounds, especially those with potent activity and low toxicity, desirable characteristics for developing new drugs. In addition, bismuth-based compounds with dual activity were also highlighted, as well as their modes of action and structure-activity relationship, among other relevant discoveries. In this way, we hope this review provides a fertile ground for rationalizing new bismuth-based drugs.
Topics: Humans; Bismuth; Anti-Bacterial Agents; Helicobacter pylori; Helicobacter Infections; Drug Therapy, Combination
PubMed: 37570891
DOI: 10.3390/molecules28155921 -
IET Nanobiotechnology Jun 2023About 50% of cancer patients receive radiation therapy. Despite the therapeutic benefits of this method, the toxicity of radiation in the normal tissues is unavoidable... (Review)
Review
About 50% of cancer patients receive radiation therapy. Despite the therapeutic benefits of this method, the toxicity of radiation in the normal tissues is unavoidable To improve the quality of radiation therapy, in addition to other methods such as IMRT, IGRT, and high radiation dose, nanoparticles have shown excellent potential when ionising radiation is applied to the target volume. Recently, bismuth-based nanoparticles (BiNPs) have become particularly popular in radiation therapy due to their high atomic numbers (Z), high X-ray attenuation coefficient, low toxicity, and low cost. Moreover, it is easy to synthesise in a variety of sizes and shapes. This study aimed to review the effects of the bismuth-based NP and its combination with other compounds, and their potential synergies in radiotherapy, discussed based on their physical, chemical, and biological interactions. Targeted and non-targeted bismuth-based NPs used in radiotherapy as radiosensitizers and dose enhancement effects are described. The results reported in the literature were categorised into various groups. Also, this review has highlighted the importance of bismuth-based NPs in different forms of cancer treatment to find the highest efficiency for applying them as a suitable candidate for various cancer therapy and future clinical applications.
Topics: Humans; Bismuth; Nanoparticles; Radiation-Sensitizing Agents; Neoplasms
PubMed: 37139612
DOI: 10.1049/nbt2.12134 -
Molecules (Basel, Switzerland) Sep 2014: Bismuth compounds have been used extensively as medicines and in particular for the treatment of gastrointestinal ailments. In addition to bismuth's well known... (Review)
Review
: Bismuth compounds have been used extensively as medicines and in particular for the treatment of gastrointestinal ailments. In addition to bismuth's well known gastroprotective effects and efficacy in treating H. pylori infection it also has broad anti-microbial, anti-leishmanial and anti-cancer properties. Aspects of the biological chemistry of bismuth are discussed and biomolecular targets associated with bismuth treatment are highlighted. This review strives to provide the reader with an up to date account of bismuth-based drugs currently used to treat patients and discuss potential medicinal applications of bismuth drugs with reference to recent developments in the literature. Ultimately this review aims to encourage original contributions to this exciting and important field.
Topics: Anti-Infective Agents; Antineoplastic Agents; Antiprotozoal Agents; Bismuth; Gastrointestinal Diseases; Humans; Molecular Structure
PubMed: 25251194
DOI: 10.3390/molecules190915258 -
Scientific Reports Jan 2023Due to its unique physical and chemical properties, bismuth is an attractive candidate for a wide range of applications such as battery anodes, radiation shielding, and...
Due to its unique physical and chemical properties, bismuth is an attractive candidate for a wide range of applications such as battery anodes, radiation shielding, and semiconductors, to name a few. This work presents the electrodeposition of mechanically stable and homogenous bismuth films at micron-scale thicknesses. A simple one-step electrodeposition process using either a pulse/reverse or direct current source yielded thick, homogenous, and mechanically stable bismuth films. Morphology, electrochemical behavior, adhesion, and mechanical stability of bismuth coatings plated with varying parameters were characterized via optical profilometry, cyclic voltammetry, electron microscopy, and tribology. Scratch testing on thick electroplated coatings (> 100 µm) revealed similar wear resistance properties between the pulse/reverse plated and direct current electroplated films. This study presents a versatile bismuth electroplating process with the possibility to replace lead in radiation shields with an inexpensive, non-toxic metal, or to make industrially relevant electrocatalytic devices.
Topics: Bismuth; Electroplating; Electrodes; Radiation Protection
PubMed: 36681686
DOI: 10.1038/s41598-023-28042-z -
International Journal of Nanomedicine 2020Here, bismuth-based nanomaterials (Bi-based NMs) are introduced as promising theranostic agents to enhance image contrast as well as for the therapeutic gain for... (Review)
Review
Here, bismuth-based nanomaterials (Bi-based NMs) are introduced as promising theranostic agents to enhance image contrast as well as for the therapeutic gain for numerous diseases. However, understanding the interaction of such novel developed nanoparticles (NPs) within a biological environment is a requisite for the translation of any promising agent from the lab bench to the clinic. This interaction delineates the fate of NPs after circulation in the body. In an ideal setting, a nano-based therapeutic agent should be eliminated via the renal clearance pathway, meanwhile it should have specific targeting to a diseased organ to reach an effective dose and also to overcome off-targeting. Due to their clearance pathway, biodistribution patterns and pharmacokinetics (PK), Bi-based NMs have been found to play a determinative role to pass clinical approval and they have been investigated extensively in vivo to date. In this review, we expansively discuss the possible toxicity induced by Bi-based NMs on cells or organs, as well as biodistribution profiles, PK and the clearance pathways in animal models. A low cytotoxicity of Bi-based NMs has been found in vitro and in vivo, and along with their long-term biodistribution and proper renal clearance in animal models, the translation of Bi-based NMs to the clinic as a useful novel theranostic agent is promising to improve numerous medical applications.
Topics: Animals; Bismuth; Humans; Metal Nanoparticles; Nanostructures; Precision Medicine; Tissue Distribution
PubMed: 33061369
DOI: 10.2147/IJN.S250001 -
Gut and Liver Nov 2022
Topics: Humans; Helicobacter pylori; Bismuth; Clarithromycin; Helicobacter Infections; Amoxicillin; Anti-Bacterial Agents; Drug Therapy, Combination; Proton Pump Inhibitors; Treatment Outcome
PubMed: 36379903
DOI: 10.5009/gnl220414 -
Journal of the American Chemical Society Sep 2022The development of unconventional strategies for the activation of ammonia (NH) and water (HO) is of capital importance for the advancement of sustainable chemical...
The development of unconventional strategies for the activation of ammonia (NH) and water (HO) is of capital importance for the advancement of sustainable chemical strategies. Herein we provide the synthesis and characterization of a radical equilibrium complex based on bismuth featuring an extremely weak Bi-O bond, which permits the in situ generation of reactive Bi(II) species. The ensuing organobismuth(II) engages with various amines and alcohols and exerts an unprecedented effect onto the X-H bond, leading to low BDFE. As a result, radical activation of various N-H and O-H bonds─including ammonia and water─occurs in seconds at room temperature, delivering well-defined Bi(III)-amido and -alkoxy complexes. Moreover, we demonstrate that the resulting Bi(III)-N complexes engage in a unique reactivity pattern with the triad of H, H, and H sources, thus providing alternative pathways for main group chemistry.
Topics: Amines; Ammonia; Bismuth; Water
PubMed: 36053726
DOI: 10.1021/jacs.2c05882