Disease relevance of Bromdimoprim

• 1H and 15N NMR studies have been undertaken on complexes of Lactobacillus casei dihydrofolate reductase (DHFR) formed with analogues of the antibacterial drug brodimoprim (2,4-diamino-5-(3', 5'-dimethoxy-4'-bromobenzyl)pyrimidine) in order to monitor interactions between carboxylate groups on the ligands and basic residues in the protein [1].
• Brodimoprim synergy against Enterococcus faecalis evaluated in vitro [2].
• Brodimoprim in acute exacerbations of chronic bronchitis: a clinical and bacteriological pilot study [3].
• The results indicate that brodimoprim is safe and effective in the treatment of acute sinusitis in adults [4].
• Efficacy and tolerability of brodimoprim in respiratory tract infections [5].

High impact information on Bromdimoprim

• 1H/15N HSQC spectra have been fully assigned for the complexes with the three brodimoprim analogues and chemical shift mapping used to explore interactions in the binding site [1].
• Both drugs may accumulate within neutrophils; however, brodimoprim does so to a greater extent [6].
• Brodimoprim did not decrease either phagocytosis or phagocyte-mediated bactericidal activity, nor did it affect oxidative burst activity, as investigated by luminol-amplified chemiluminescence [7].
• These results suggest that once-daily treatment with brodimoprim represents safe and effective therapy for adults with acute bacterial sinusitis [8].
• In vitro activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with brodimoprim and dapsone, against Mycobacterium leprae [9].

Chemical compound and disease context of Bromdimoprim

• Eighty adult outpatients with acute sinusitis were randomly assigned to receive 200 mg of brodimoprim once daily or 750 mg of amoxicillin thrice daily for seven to 10 days [4].
• Against a range of strains of the Enterobacteriaceae trimethoprim was slightly more active, although in an in vivo murine model brodimoprim had a significantly better cure rate [10].
• The objective of the study was the comparison of the efficacy and tolerability of brodimoprim to those of erythromycin in children with acute tonsillitis or bronchitis [11].
• OBJECTIVE: To compare efficacy and tolerability of brodimoprim tablets with doxycycline tablets in adults with acute sinusitis [12].
• Eighty adult patients affected by acute bacterial otitis media were selected and randomized into two balanced groups of treatment: 1) brodimoprim 200 mg tablets at the dosage of 2 tablets in single dose on the first day and one tablet on the following days; 2) josamycin 500 mg tablets at the dosage of 3 tablets/day [13].

Biological context of Bromdimoprim

• Pharmacokinetics of brodimoprim [14].
• The fact that brodimoprim interferes with the expression of some virulence traits, in particular with adherence, at sub-MIC levels may assist the drug in eradicating respiratory pathogens from the epithelial lining, thus diminishing the probability of reinfection [15].
• Pharmacokinetic profile of brodimoprim: oral bioavailability and penetration into interstitial fluid [16].
• No significant effects of both diaminopyrimidines on chemotaxis and phagocytic activity of PMNs have been observed while both brodimoprim and trimethoprim enhanced the oxidative burst [17].
• High molecular weight low-copy F'lac, and low molecular weight high-copy pHSG298 plasmids were eliminated from E.coli treated with sub-MIC concentrations of brodimoprim [15].

Anatomical context of Bromdimoprim

• Brodimoprim concentrations in bronchial mucosa, bronchial secretions and middle ear effusions [18].
• Brodimoprim: effects of subminimal inhibitory concentrations on virulence traits of respiratory and urinary tract pathogens, and on plasmid transfer and stability [15].
• The apparent volume of distribution (V beta/F) was high (approximately 1.5 l/kg) and reflects the good penetration of brodimoprim into most body fluids and tissues [14].
• A synergistic activity between the host immune system and the direct antimicrobial action of brodimoprim may occur while using this diaminopyrimidine in vivo [17].
• In safety pharmacological tests brodimoprim showed no significant activity in the cardiovascular, autonomic neuroeffector or central nervous systems [19].

Associations of Bromdimoprim with other chemical compounds

• Correlation of trimethoprim and brodimoprim physicochemical and lipid membrane interaction properties with their accumulation in human neutrophils [6].
• Thus the efficacy of brodimoprim OD appears comparable to that of norfloxacin BID in the treatment of urinary tract infections [20].

Gene context of Bromdimoprim

• Further milestones in the application of antimicrobial DHFR inhibitors were the introduction of TMP alone in 1972, the launch of a new combination of tetroxoprim, a close TMP-analog, with sulfadiazine, and the successful clinical trials with brodimoprim, which proved clinically efficacious and safe with once-daily low dose monotherapy [21].
• Based on both IC50 and Ki values, brodimoprim (BDP) was often found to be two- to threefold more effective than trimethoprim (TMP) against a great variety of different bacterial dihydrofolate reductases (DHFR) [22].
• The toxicology and safety pharmacology of brodimoprim (Ro 10-5970), a new dihydrofolate reductase inhibitor for antimicrobial chemotherapy, are reported [19].

Analytical, diagnostic and therapeutic context of Bromdimoprim

• Determination of brodimoprim and its hydroxy metabolite in human plasma, blood and urine by high-performance liquid chromatography [23].
• Side effects were reported in 5 patients treated with brodimoprim and in 3 patients in the control group [24].
• The acute toxicity of brodimoprim after oral administration is low [19].
• The efficacy and tolerability of brodimoprim in acute lower respiratory tract infections was tested in controlled clinical trials in comparison with different classes of antibiotics [5].
• Brodimoprim resulted more efficacious in the reduction of symptoms, especially hypoacusis and tinnitus (p < 0.05 between treatments); tympanometry showed a higher number of normalizations in the brodimoprim group, without significant differences between treatments [25].

References