Amoxicillin/clavulanic acid-warfarin drug interaction: a randomized controlled trial.
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SUBMITTER: Zhang Q
PROVIDER: S-EPMC3040543 | biostudies-literature | 2011 Feb
REPOSITORIES: biostudies-literature
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Amoxicillin/clavulanic acid-warfarin drug interaction: a randomized controlled trial.
Zhang Qian Q Simoneau Guy G Verstuyft Celine C Drouet Ludovic L Bal dit Sollier Claire C Alvarez Jean-Claude JC Rizzo-Padoin Nathalie N Bergmann Jean Francois JF Becquemont Laurent L Mouly Stéphane S
British journal of clinical pharmacology 20110201 2
<h4>Aims</h4>To investigate whether an interaction exists between amoxicillin/clavulanic acid (amoxiclav) and warfarin in patients treated with stable oral anticoagulant therapy.<h4>Methods</h4>In a double-blind, cross-over, placebo-controlled study, 12 patients on stable warfarin therapy, received a 7 day amoxiclav regimen or placebo.<h4>Results</h4>The mean maximum increase in INR observed was 0.22 ± 0.3 with amoxiclav vs. 0.24 ± 0.6 with placebo (P=0.94). The day 7-day 1 factor II, R(-) and S ...[more]
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Project description:Effective therapeutic regimens for the treatment of tuberculosis (TB) are limited. They are comprised of multiple drugs that inhibit the essential cellular pathways in Mycobacterium tuberculosis (Mtb). The present study investigates an approach which enables a combination of Amoxicillin-Clavulanic acid (AMC) and a repurposed drug for its synergistic effect towards TB treatment. We identified Diosmin (DIO), by targeting the active site residues of L,D-transpeptidase (Ldt) enzymes involved in Mtb cell wall biosynthesis by using a structure-based drug design method. DIO is rapidly converted into aglycone form Diosmetin (DMT) after oral administration. Binding of DIO or DMT towards Ldt enzymes was studied using molecular docking and bioassay techniques. Combination of DIO (or DMT) and AMC exhibited higher mycobactericidal activity against Mycobacterium marinum as compared to individual drugs. Scanning electron microscopy study of M. marinum treated with AMC-DIO and AMC-DMT showed marked cellular leakage. M. marinum infected Drosophila melanogaster fly model showed an increased fly survival of ~60% upon treatment with a combination of AMC and DIO (or DMT). Finally, the enhanced in vitro antimicrobial activity of AMC-DIO was validated against Mtb H37Ra and a MDR clinical isolate. Our results demonstrate the potential for AMC and DIO (or DMT) as a synergistic combination for the treatment of TB.
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2024-06-13 | PXD046061 | Pride
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