China
Africa
Explore chapters and articles related to this topic
Fleroxacin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Multiple once daily doses of either oral or i.v. fleroxacin 400 mg are bacteriologically effective in 84–96% of selected patients with acute-on-chronic bronchitis and 84–100% with nonpneumococcal pneumonia or tracheobronchitis (Chodosh, 1993; Farkas, 1993; Ulmer, 1993; Balfour et al., 1995). However, these promising results are somewhat misleading as they do not necessarily reflect the likely outcome if fleroxacin is used as empiric therapy in these situations, since most studies excluded cases with fleroxacin-resistant pathogens (e.g. S. pneumoniae) or in which no pathogen was isolated. In fact, only 27–46% of enrolled patients were subsequently analyzed for antibiotic efficacy in these studies. Nevertheless, fleroxacin compared favorably with amoxicillin for exacerbations of chronic bronchitis, with clinical cure rates of 90–95% versus 76–82%, respectively (Chodosh, 1993; Ulmer, 1993). For nonpneumococcal lower respiratory tract infections, i.v. fleroxacin 400 mg daily resulted in clinical cure in 88% of patients versus 82% for ceftazidime, although there was insufficient statistical power to allow the statement that the two treatment regimens were equivalent (Farkas, 1993). Thus, in certain clinical situations, especially in which the pathogen is known to be sensitive to fluoroquinolones, fleroxacin may be a convenient and effective antibiotic choice. If pneumococcal infection is considered likely, an alternative agent with better activity against this pathogen should be chosen.
The discovery and development of transmembrane serine protease 2 (TMPRSS2) inhibitors as candidate drugs for the treatment of COVID-19
Published in Expert Opinion on Drug Discovery, 2022
Christiana Mantzourani, Sofia Vasilakaki, Velisaria-Eleni Gerogianni, George Kokotos
Baby et al. used the human plasma kallikrein (PDB ID: 5TJX), identified with BLAST tool, as the template to build the homology model of TMPRSS2 protein. Schrödinger Prime Module was employed for the construction of the model, which further modified with Refine Loops software and evaluated accordingly [103]. Schrödinger’s High Throughput Virtual Screening was employed to dock ~2800 FDA-acquiesced molecules in TMPRSS2 and ACE2, for which the receptor grid was created based on the co-crystalized ligand. Their calculations resulted in a number of drugs that demonstrated a promising binding mode, including valrubicin, lopinavir, fleroxacin, alvimopan, arbekacin, and dequalinium. For these compounds, molecular dynamics in Maestro Desmond was accomplished and suggested a superiority of valrubicin and lopinavir in their formation of a stable complex with the proteins. The main interactions formed in these complexes were hydrophobic and hydrophilic with residues such as Trp461, Trp461, Lys300.
A Review of Immunomodulatory Effects of Fluoroquinolones
Published in Immunological Investigations, 2021
Shokrollah Assar, Reza Nosratabadi, Hossein Khorramdel Azad, Javad Masoumi, Mahshad Mohamadi, Gholamhossein Hassanshahi
FQs are a broad range of synthetic antibiotics that are being widely consumed for their clinical features, including their availability, wide therapeutic index, and reasonable level of resistance (Mitscher 2005). These antimicrobial compounds exert their effects by entering into the cytosol of bacteria, binding to topoisomerase II (DNA gyrase) and IV, and inactivating these enzymes, especially in prokaryotes (Aldred et al. 2013). One of the distinctive features making FQs different from other natural antibiotics is their inherent physicochemical properties that help them to penetrate into the lipid bilayer of gram-negative bacteria to exert antimicrobial effects (Dalhoff and Schubert 2016; Idowu and Schweizer 2017). Given the broad range of antimicrobial activities, FQs are classified into four generations. The first generation includes oxolinic acid, inoxacin, flumequine, pefloxacin, rosoxacin, and nalidixic acid; the second generation encompasses ciprofloxacin, fleroxacin, lomefloxacin, nadifloxacin, norfloxacin, ofloxacin, and rufloxacin; the third generation is composed of balofloxacin, grepafloxacin, levofloxacin, pazufloxacin, sparfloxacin, and temafloxacin; and the fourth generation involves clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, prulifloxacin, and besifloxacin (Sousa et al. 2014). Research reports that these synthetic compounds, in addition to serving as antimicrobial agents, affect the immune system and mediators involved in immune responses (Dalhoff 2005).
Prediction of volume of distribution in preclinical species and humans: application of simplified physiologically based algorithms
Published in Xenobiotica, 2019
Prashant B. Nigade, Jayasagar Gundu, K. Sreedhara Pai, Kumar V. S. Nemmani, Rashmi Talwar
The values of Vss of 27 structurally unrelated compounds (4 acidic; 4 neutral, 1 zwitterionic, 5 weak base and 13 strong basic compounds) predicted based on Equation (7) were compared with corresponding in vivo experimentally derived values sourced from published literature (Table 3 and 5). Human Vss of caffeine, cimetidine and fleroxacin were estimated using experimental values of lung- and muscle-Kps, whereas for the remaining 24 compounds, these inputs were estimated using rat Kp data as a reference species and derived interspecies scaling factors SF1 and SF2 (Equation (8)). The human Vss of ∼93% (25 out of 27) compounds was predicted within two-fold of the experimental values in human. The predicted human Vss of disopyramide and fentanyl was within three-fold of the experimental values (Table 5; Figure 1).