Lefamulin acetate
(Synonyms: 醋酸来法莫林,BC-3781 acetate) 目录号 : GC39163
A pleuromutilin antibiotic
Cas No.:1350636-82-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Lefamulin is a pleuromutilin antibiotic.1 It is active against methicillin-resistant S. aureus (MRSA), S. pyogenes, E. faecium, H. influenzae, M. catarrhalis, L. pneumonophilia, C. pneumoniae, and M. pneumoniae (MIC50s = 0.006-1 ?g/ml). Lefamulin is also active against fluoroquinolone- and macrolide-resistant strains of N. gonorrhoeae (MIC90s = 1 mg/L for all). In vivo, lefamulin (10-40 mg/kg) reduces the number of colony-forming units (CFUs) in a mouse model of S. pneumoniae thigh infection.2 It also reduces LPS-induced production of TNF-α, IL-6, IL-1β, and GM-CSF, bronchoalveolar lavage fluid (BALF) neutrophil infiltration, and lung matrix metalloproteinase-9 (MMP-9) levels in a mouse model of LPS-induced neutrophilia.3 Formulations containing lefamulin have been used in the treatment of community-acquired bacterial pneumonia (CABP).
1.Veve, M.P., and Wagner, J.L.Lefamulin: Review of a promising novel pleuromutilin antibioticPharmacotherapy38(9)935-946(2018) 2.Wicha, W.W., Craig, W.A., and Andes, D.In vivo pharmacodynamics of lefamulin, the first systemic pleuromutilin for human use, in a neutropenic murine thigh infection modelJ. Antimicrob. Chemother.74(Suppl 3)iii5-iii10(2019) 3.Hafner, M., Paukner, S., Wicha, W.W., et al.Anti-inflammatory activity of lefamulin versus azithromycin and dexamethasone in vivo and in vitro in a lipopolysaccharide-induced lung neutrophilia mouse modelPLoS One16(9)e0237659(2022)
| Cas No. | 1350636-82-6 | SDF | |
| 别名 | 醋酸来法莫林,BC-3781 acetate | ||
| Canonical SMILES | CC(O)=O.C[C@@H]1C23[C@](C(CC3)=O)([H])C([C@H](OC(CS[C@H]4[C@@H](C[C@H](N)CC4)O)=O)C[C@](C=C)(C)[C@H]1O)([C@H](C)CC2)C | ||
| 分子式 | C30H49NO7S | 分子量 | 567.78 |
| 溶解度 | DMSO: ≥ 100 mg/mL (176.12 mM); Water: < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7612 mL | 8.8062 mL | 17.6125 mL |
| 5 mM | 0.3522 mL | 1.7612 mL | 3.5225 mL |
| 10 mM | 0.1761 mL | 0.8806 mL | 1.7612 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Lefamulin vs moxifloxacin for community-acquired bacterial pneumonia
Medicine (Baltimore) 2020 Jul 17;99(29):e21223.PMID:32702892DOI:10.1097/MD.0000000000021223.
Lefamulin is a novel pleuromutilin antibiotic with potent in vitro activity against key community-acquired bacterial pneumonia (CABP) pathogens. However, the clinical efficacy and safety of Lefamulin for treating CABP remains unclear.An integrated analysis of 2 phase III trials investigating the clinical efficacy and safety of Lefamulin vs moxifloxacin in the treatment of CABP was conducted.A total of 1289 patients (Lefamulin group: 646 and moxifloxacin group: 643) were included in this analysis. The early clinical response rate was 89.3% and 90.5% among Lefamulin and moxifloxacin group, respectively. Lefamulin was noninferior to moxifloxacin (89.3% vs 90.5%, RR: 0.99, 95% CI: 0.95-1.02, I = 0%). In terms of clinical response at test of cure, no significant difference was observed between the Lefamulin and moxifloxacin groups (for modified intention to treat population, RR: 0.98, 95% CI: 0.94-1.02, I = 0%; for clinically evaluable population, RR: 0.96, 95% CI: 0.93-1.00, I = 0%). In the subgroup analysis, the early clinical response rate at early clinical assessment and clinical response rate at test of cure of Lefamulin was similar to that of moxifloxacin across different subgpopulations and all baseline CABP pathogens. Lefamulin was associated with a similar risk of adverse events as moxifloxacin.Clinical efficacy and tolerability for Lefamulin in the treatment of CABP were similar to those for moxifloxacin.
Lefamulin: The First Systemic Pleuromutilin Antibiotic
Ann Pharmacother 2020 Dec;54(12):1203-1214.PMID:32493034DOI:10.1177/1060028020932521.
Objective: To review the pharmacology, microbiology, efficacy, and safety of Lefamulin. Data sources: A literature search was performed using PubMed and Google Scholar (2010 to end-April 2020) with the search terms BC-3781 and Lefamulin. Other resources included abstracts presented at recent conferences, prescribing information, and the manufacturer's and Food and Drug Administration websites. Study selection and data extraction: All relevant English-language articles of studies assessing the efficacy and safety of Lefamulin were included. Data synthesis: Lefamulin is a pleuromutilin antibiotic with activity against Staphylococcus aureus, Streptococcus pneumoniae, and atypical bacteria. Lefamulin, given at the dose of 150 mg intravenously or 600 mg orally on an empty stomach every 12 hours for 5 to 7 days, was proven noninferior to moxifloxacin for the treatment of community-acquired bacterial pneumonia (CABP). Common adverse reactions include injection site reactions, hepatic enzyme elevation, gastrointestinal upset, hypokalemia, insomnia, and headache. Lefamulin is associated with QT prolongation, and concomitant use with CYP3A substrates that prolong the QT interval is contraindicated. Lefamulin may cause fetal harm. Relevance to patient care and clinical practice: Lefamulin is a novel antibiotic with a unique mechanism of action. It represents an alternative option to β-lactams and macrolides in the treatment of adults with CABP and an alternative option to amoxicillin and doxycycline in the outpatient setting given the rise in resistance to macrolides and safety concerns with fluoroquinolones. Nausea, vomiting, and diarrhea may limit the tolerability of the oral formulation. Conclusions: Lefamulin is the first systemic pleuromutilin antibiotic that has proven safe and effective for adults with CABP.
Lefamulin: Review of a Promising Novel Pleuromutilin Antibiotic
Pharmacotherapy 2018 Sep;38(9):935-946.PMID:30019769DOI:10.1002/phar.2166.
The emergence and spread of antimicrobial resistance have led to a global public health emergency requiring development of new antimicrobial classes. Lefamulin (formally BC-3781) is a novel pleuromutilin antibiotic currently undergoing Food and Drug Administration review for community-acquired bacterial pneumonia (CABP) as intravenous (IV) and oral (PO) formulations. Although pleuromutilin antibiotics were first developed in the 1950s, Lefamulin is the first to be used for systemic treatment of bacterial infections in humans. Lefamulin exhibits a unique mechanism of action through inhibition of protein synthesis by binding to the peptidyl transferase center of the 50S bacterial ribosome, thus preventing the binding of transfer RNA for peptide transfer. Lefamulin displays activity against gram-positive and atypical organisms associated with CABP (i.e., Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydophila pneumoniae), with an expanded gram-positive spectrum including Staphylococcus aureus (i.e., methicillin-resistant, vancomycin-intermediate, and heterogeneous strains) and vancomycin-resistant Enterococcus faecium. Lefamulin was also shown to retain activity against multidrug-resistant Neisseria gonorrhoeae and Mycoplasma genitalium. Lefamulin exhibits time-dependent killing, and the pharmacodynamic target best associated with antibacterial activity is ƒAUC0-24 /MIC (minimum inhibitory concentration [MIC]). Preclinical and phase II trials indicate that Lefamulin concentrates in lung tissue are well tolerated at an IV dose of 150 mg twice/day over 1 hour or a PO dose of 600 mg twice/day, and preliminary phase III data suggest similar efficacy when compared with moxifloxacin with or without linezolid in CABP. Documented resistance and cross-resistance with other gram-positive antibacterials remains low. Additional published in vitro, in vivo, and preclinical trial data suggest further exploration of Lefamulin in various infectious disease states (e.g., acute bacterial skin and skin structure infections, and sexually transmitted infections). This review discusses the pertinent bacterial spectrum of activity, preclinical and ongoing clinical data, and potential roles in therapy for Lefamulin.
Clinical use of Lefamulin: A first-in-class semisynthetic pleuromutilin antibiotic
J Intern Med 2022 Jan;291(1):51-63.PMID:34425035DOI:10.1111/joim.13378.
Lefamulin is a novel antibiotic agent within the pleuromutilin derivative class approved for the treatment of community-acquired bacterial pneumonia (CABP) by the United States Food and Drug Administration and the European Commission in 2019 and 2020, respectively. The objective of this article is to provide a summary of clinically relevant data underlying Lefamulin and to provide recommendations for its place in therapy. In vitro data establish Lefamulin's activity against a number of Gram-positive, Gram-negative and atypical organisms relevant in the treatment of CABP, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, Mycoplasma pneumoniae and Chlamydophila pneumoniae. Two phase-3 studies, the Lefamulin Evaluation Against Pneumonia trials, established non-inferiority of Lefamulin against moxifloxacin in the treatment of CABP, including the sequential transition from intravenous to oral therapy and across a broad set of patient demographics and severities. Pooled and post hoc analyses have confirmed these effects for a variety of subgroups and secondary endpoints. Real-world study data post-approval have largely not yet emerged for Lefamulin, and there is a need for further investigation into safety/efficacy for off-label indications such as acute bacterial skin and skin structure infections and sexually transmitted infections. Further data regarding tolerability, particularly with long-term use, as well as the emergence of resistance over time, are still undefined.
An overview of Lefamulin for the treatment of community acquired bacterial pneumonia
Expert Opin Pharmacother 2020 Apr;21(6):629-636.PMID:31958020DOI:10.1080/14656566.2020.1714592.
Introduction: Lefamulin is a novel antibiotic that belongs to the pleuromutilin class with excellent activity against all microorganisms, including atypical pathogens, that cause community-acquired pneumonia (CAP). Areas covered: This article reviews the spectrum of activity, the main pharmacokinetic and pharmacodynamic characteristics of Lefamulin as well as its clinical efficacy and safety in the treatment of CAP in adult patients. Expert opinion: The clinical efficacy of Lefamulin in patients with non severe CAP has been demonstrated in 2 randomized clinical trials. Precisely one of the limitations of the phase 3 trials is that the proportion of severe CAP cases is very low. Its particular mechanism of action, affecting ribosomal protein synthesis, provides a low probability of cross-resistance to other commonly used antibiotics in CAP. These findings, together with the antimicrobial activity of Lefamulin, its pharmacokinetic parameters and safety profile make it a good alternative for outpatient treatment of CAP. In patients hospitalized with CAP, Lefamulin can be used as a potential oral step-down agent after an intravenous regimen with beta-lactams, or as a therapeutic alternative in patients with β-lactam allergies.