Hydrolytic Enzymes for the Synthesis of Pharmaceuticals
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Levofloxacin is a potent fluoroquinolone antibacterial agent used in the treatment of pneumonia, sinusitis or urinary tract infections among others. Rhizomucor miehei lipase (RML) has been efficiently applied in the hydrolysis of racemic 1-(2,3-difluoro-6-nitrophenoxy)propan-2-yl acetate, (Scheme 9.8), leading to the formation of the enantiopure (R)-alcohol in 45% yield and the remaining (R)-acetate in 84% ee after 53 h at 30°C (López-Iglesias et al., 2015). Alternatively, the same alcohol and the homologue amine have been produced in higher-yielding processes starting from prochiral ketones through bioreduction or biotransamination experiments, respectively (Mourelle-Insua et al., 2016). RML-catalysed hydrolysis of a racemic ester for the production of a Levofloxacin precursor.
Levofloxacin
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 in Kucers’ The Use of Antibiotics, 2017
Levofloxacin (Levaquin, Iquix, Quixin) is a fluoroquinolone that is the optical S-(–) isomer of ofloxacin. It was originally developed by the Daiichi Seiyaku Pharmaceutical Co. Ltd. in Japan. Its chemical formula is (–)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido [1,2,3-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate (Figure 104.1), and it has a molecular weight of 370 daltons. Ofloxacin is a racemic mixture of two optical isomers, but the S-isomer has antibacterial activity 32- to 128-fold greater than that of the R-isomer, and thus most of the antibacterial activity of ofloxacin is due to the S-isomer, which constitutes levofloxacin. Levofloxacin, like ofloxacin and other fluoroquinolones, is an inhibitor of the bacterial type II topoisomerases DNA gyrase and DNA topoisomerase IV. Levofloxacin was developed to take advantage of its increased antibacterial potency and a potentially improved toxicity profile (Davis and Bryson, 1994; Inage et al., 1992; Tanaka et al., 1992; Une et al., 1988).
Shorter Course Antibiotic Therapy (SCAT): Principles, Current Data, and Caveats
Robert C. Owens, Lautenbach Ebbing in Antimicrobial Resistance, 2007
Because levofloxacin is a concentration-dependent antibiotic in which therapeutic success is associated with the AUC/MIC and Cmax/MIC, higher doses may be more effective in helping prevent resistance (49,50). Also, the mean epithelial lining fluid concentration was 9.9 mg/mL with the 500 mg low dose levofloxacin versus 22.1 mg/mL for the 750 mg group. Higher dose and SCAT for 5 days may also increase compliance and prevent the emergence of resistance. Higher doses of levofloxacin in this study were not associated with greater adverse effects than in the lower dose control group. Notably, the overall mortality rate was increased twofold in the longer course 500 mg group (3.4% vs. 1.9%), but the difference was not statistically significant.
Ameliorative effects of Moringa oleifera leaf extract on levofloxacin-induced hepatic toxicity in rats
Published in Drug and Chemical Toxicology, 2020
Ayman Samir Farid, Ahmed Medhat Hegazy
Levofloxacin is a third-generation fluoroquinolone antibiotic. It has broad-spectrum activity against Gram-positive and Gram-negative bacteria as well as certain other pathogens such as Mycobacteria spp., Mycoplasma, Chlamydia, and Legionella (Fish and Chow 1997). The effectiveness of Levofloxacin against infections of the respiratory tract, skin and genitourinary tract has been demonstrated (Croom and Goa 2003). Levofloxacin triple therapy containing Levofloxacin, a proton pump inhibitor, and amoxicillin has been effective for the treatment of Helicobacter pylori infection for more than 10 years (Malfertheiner et al.2012, Nista et al.2003). Levofloxacin and other fluoroquinolones produce serious adverse effects more frequently than other broad-spectrum antibacterial drugs (Stahlmann and Lode 2013). The most common side effects are abdominal pain, diarrhea, vomiting, nausea, dizziness, and rash (Ceydilek et al.2005). Hepatotoxicity, phototoxicity, cardiotoxicity, and central nervous system side effects are less frequent. Increases in liver function tests and liver failure (Ceydilek et al. 2005, Gulen et al.2015, Yagawa 2001) are mentioned.
Formulation of sustained release bioadhesive minitablets containing solid dispersion of levofloxacin for once daily ocular use
Published in Pharmaceutical Development and Technology, 2019
Ahmed Abd El-Bary, Howida Kamal Ibrahim, Balqees Saeed Haza’a, Ibrahim Al Sharabi
Levofloxacin is a third-generation fluoroquinolone antibiotic with a broad spectrum against both Gram-positive and Gram-negative bacteria. The drug is available as 0.5% eye drops for the treatment of ocular bacterial infections including conjunctivitis and keratitis (Pawar et al. 2013). Similar to all ophthalmic drops, more than 90% of the topically applied levofloxacin is lost, and frequent administration is required to maintain the therapeutic level of the drug in the eye (Duxfield et al. 2016). Several levofloxacin containing formulations for once or twice daily administration were described in the literature (i.e. ocuserts, microspheres, nanoparticles, and in situ gel) (Gorle and Gattani 2010; Cai et al. 2011; Gupta et al. 2011, 2015; Saher et al. 2016). However, all of these formulations do not match minitablets in terms of cost-effectiveness, ease of manufacturing, ease of application, reliable drug release, and low risk of flushing out (Moosa et al. 2014).
Diagnosis and Treatment of 75 Patients with Idiopathic Lobular Granulomatous Mastitis
Published in Journal of Investigative Surgery, 2019
Jieqing Li
Although glucocorticoid and methotrexate are mainly used drugs to treat IGLM24–26, either alone or in the combination, patients in this study were not treated with the two drugs. A report27 advocated the use of antibiotics before and after surgery. However, the effect of using antibiotics may not be always good; for example, 31 patients in this study received antibiotics treatment before they were diagnosed in our hospital, but ineffective result of antibiotics was shown in 23 of them. Eight cases used antibiotic treatment and the effect is limited to lump and skin redness reduction, suggesting that IGLM may be complicated by pathogen infection, and the use of antibiotics helped to eliminate the relevant symptoms. Fifteen patients, who did not receive surgical treatment, were treated with symptomatic treatment. Among these 15 patients, 2 patients did not take any treatment, and were discharged after the diagnosis was confirmed; 13 patients were treated with levofloxacin for 7–10 days, and then discharged after the symptoms improved. There is no difference in prognosis in this group of patients regardless of whether the use of antibiotics or not. Currently, there is no evidence supporting the use of antibiotics for IGML. In our future management, we will take a more rational and evidence-based approach in the use of antibiotics therapy for IGML.
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- Tuberculosis
- Helicobacter Pylori
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