Garenoxacin (BMS284756)
(Synonyms: 加雷沙星; BMS284756) 目录号 : GC33972
A quinolone antibiotic
Cas No.:194804-75-6
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
Garenoxacin is a quinolone antibiotic.1 It is active against a variety of Gram-positive and Gram-negative bacteria (MIC90s = 0.025-6.25 and 0.0125-100 ?g/ml, respectively). Garenoxacin inhibits E. coli DNA gyrase supercoiling and S. aureus topoisomerase IV decatenation activities (IC50s = 0.17 and 2.19 mg/L, respectively).2 It is selective for S. aureus topoisomerase IV over human topoisomerase II (IC50 = 509.7 ?g/L). Garenoxacin is efficacious against systemic quinolone-resistant S. aureus infection and pneumonia induced by the penicillin-resistant S. pneumoniae clinical isolate D-979 in mice (ED50s = 0.0189 and 0.0278 mg/animal, respectively).1
1.Takahata, M., Mitsuyama, J., Yamashiro, Y., et al.In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinoloneAntimicrob. Agents Chemother.43(5)1077-1084(1999) 2.Lawrence, L.E., Wu, P., Fan, L., et al.The inhibition and selectivity of bacterial topoisomerases by BMS-284756 and its analoguesJ. Antimicrob. Chemother.48(2)195-201(2001)
| Cas No. | 194804-75-6 | SDF | |
| 别名 | 加雷沙星; BMS284756 | ||
| Canonical SMILES | O=C(C1=CN(C2CC2)C3=C(C=CC(C4=CC5=C([C@@H](C)NC5)C=C4)=C3OC(F)F)C1=O)O | ||
| 分子式 | C23H20F2N2O4 | 分子量 | 426.41 |
| 溶解度 | DMSO: 1 mg/ml | 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 | 2.3452 mL | 11.7258 mL | 23.4516 mL |
| 5 mM | 0.469 mL | 2.3452 mL | 4.6903 mL |
| 10 mM | 0.2345 mL | 1.1726 mL | 2.3452 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。
Geographic variations in Garenoxacin (BMS284756) activity tested against pathogens associated with skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (2000)
Diagn Microbiol Infect Dis 2002 Aug;43(4):303-9.PMID:12151191DOI:10.1016/s0732-8893(02)00415-7.
The antimicrobial activity of garenoxacin, a des-(6)F quinolone (formally BMS284756 and T-3811), was evaluated against 2,537 skin and soft tissue infection (SSTI) isolates from the SENTRY Antimicrobial Surveillance Program. Strains isolated in 2000 from Europe, North and Latin America were tested at a central laboratory using reference broth microdilution methods. The rank order of the seven most frequent SSTI pathogens was: Staphylococcus aureus (39.9%), Pseudomonas aeruginosa (12.1%), Escherichia coli (9.7%), Enterococcus spp. (7.7%), Klebsiella spp. (5.8%), Enterobacter spp. (5.6%) and coagulase-negative staphylococci (CoNS; 4.2%). Garenoxacin exhibited a four-fold greater activity (MIC(90), 0.06 microg/ml) compared to levofloxacin (MIC(90), 0.25 microg/ml) against oxacillin-susceptible S. aureus; and oxacillin-resistant staphylococci were more susceptible to garenoxacin (>/=90.5%) at Europe > North America). Continued development of garenoxacin as a treatment of pathogens that commonly cause SSTIs appears to be warranted.
Clinical studies of Garenoxacin
Int J Antimicrob Agents 2008 Dec;32(6):468-74.PMID:18790608DOI:10.1016/j.ijantimicag.2008.06.032.
Garenoxacin mesylate hydrate (GRN) is a novel oral des-fluoro(6) quinolone with potent antimicrobial activity against common respiratory pathogens, including resistant strains. It has favourable pharmacokinetic profiles for maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC), with good penetration into sputum and otorhinolaryngological tissues. In clinical studies, the efficacy of GRN ranged from 92% to 96% in patients with bacterial pneumonia, mycoplasma pneumonia, chlamydial pneumonia and acute bronchitis. Efficacy was 85% in acute infectious exacerbations of chronic respiratory disease and ranged from 81% to 95% in otorhinolaryngological infections. Bacterial eradication was 90.9% for Staphylococcus aureus, 99.2% for Streptococcus pneumoniae, 98.2% for Haemophilus influenzae, 96.6% for Moraxella catarrhalis, 100% for penicillin-resistant S. pneumoniae, 100% for beta-lactamase-negative ampicillin-resistant H. influenzae and beta-lactamase-positive H. influenzae, and 96.2% for beta-lactamase-positive M. catarrhalis. Garenoxacin concentrations in plasma and tissues using GRN 400mg once a day were higher than the MIC90 (minimum inhibitory concentration for 90% of the organisms) of major causative pathogens. The trough concentration (Cmin) in plasma was 1.92 microg/mL, a level that was higher than the mutant prevention concentration, suggesting that GRN is unlikely to induce the selection of resistant strains during treatment. In clinical studies, GRN did not produce class adverse effects of fluoroquinolones such as QTc prolongation, blood glucose abnormality or severe liver damage. No serious adverse events were observed during the trials. The results indicate that GRN is very effective in treating patients with upper and lower respiratory tract infections.
Pharmacokinetic study of Garenoxacin in severe renal failure patients
Jpn J Antibiot 2015 Jun;68(3):141-50.PMID:26349115doi
Garenoxacin is a type of fluoroquinolone antibacterial agents. Previous studies have suggested that Garenoxacin 400 mg once daily dose is appropriate for patients with normal to moderate renal disfunction against common bacteria of respiratory infections. However, limited information has been obtained in terms of treatment for severe renal failure patients, such as hemodialysis patients, with this drug. Twenty severe renal failure patients with respiratory infection received single Garenoxacin dose (200 mg and 400 mg). By measuring blood concentration of Garenoxacin, pharmacodynamics parameters, such as the peak plasma concentration (C(max)) and the area under the concentration curve (AUC), were calculated with NONMEM. After single dose of Garenoxacin, C(max) at the 200 and 400 mg doses were within the range of 2.9 ± 0.6 and 6.0 ± 1.0 μg/mL, respectively. The corresponding values for AUC at the 200 and 400 mg doses were within the ranges of 62.3 ± 11.9 and 128.0 ± 12.5 μg x hr/mL, respectively. The mean half-life (T½) for Garenoxacin appeared to be independent of dose (13.9 ± 2.2hr and 13.7 ± 1.9 hr at the 200 and 400 mg dose). There were no serious adverse events suspected to be related with Garenoxacin. Consequently, for severe renal failure patients, the 400 mg once daily Garenoxacin dose was expected to be effective against common bacteria of respiratory infections.
Multiple-dose safety and pharmacokinetics of oral Garenoxacin in healthy subjects
Antimicrob Agents Chemother 2003 Jul;47(7):2256-63.PMID:12821477DOI:10.1128/AAC.47.7.2256-2263.2003.
Garenoxacin (T-3811ME, BMS-284756) is a novel des-F(6) quinolone that has been shown to be effective in vitro against a wide range of clinically important pathogens, including gram-positive and gram-negative aerobes and anaerobes. This study was conducted to evaluate the safety and tolerability of multiple oral doses (100 to 1200 mg/day) of Garenoxacin in healthy subjects and to determine its multiple-dose pharmacokinetics. Forty healthy male and female subjects (18 to 45 years of age) were enrolled in this randomized, double-blind, placebo-controlled, sequential, multiple- and ascending-dose study. Each subject received a once-daily oral dose of Garenoxacin (100, 200, 400, 800, or 1200 mg) or a placebo for 14 days. Blood and urine samples were collected for measurements of Garenoxacin by validated liquid chromatography with dual mass spectrometry, and plasma Garenoxacin concentration-time data were analyzed by noncompartmental methods. The effects of Garenoxacin on Helicobacter pylori, psychometric test performance, and electrocardiograms were assessed, as was drug safety. Over the 14 days of dosing, geometric mean peak concentrations of Garenoxacin in plasma (C(max)) at the 100- and 1200-mg doses were within the ranges of 1.2 to 1.6 and 16.3 to 24 microg/ml, respectively. The corresponding values for the geometric mean area under the concentration-time curve over the dosing interval (AUC(tau)) for Garenoxacin in plasma at the 100- and 1200-mg doses were within the ranges of 11.5 to 15.7 and 180 to 307 microg. h/ml, respectively. Increases in systemic exposure to Garenoxacin in terms of AUC and C(max) were approximately dose proportional over the 100- to 400-mg dose range but demonstrated increases that were somewhat greater than the dose increments at the 800- and 1200-mg doses. Median values for the time to achieve C(max) were in the range of 1.13 to 2.50 h for all doses. The mean elimination half-life for Garenoxacin in plasma appeared to be independent of dose and ranged from 13.3 to 17.8 h (day 14). Approximately 30 to 50% of an administered Garenoxacin dose was excreted unchanged in the urine. At doses of 100 to 400 mg, steady-state concentrations of Garenoxacin in plasma appeared to be attained by the fourth dose. Multiple oral doses of Garenoxacin were well tolerated and did not demonstrate clinically significant effects on QT(c) or psychometric test results. Garenoxacin administered alone for 14 days at doses of >or=400 mg demonstrated activity against H. pylori. These results suggest that multiple once-daily oral doses of Garenoxacin of up to 1200 mg are safe and well tolerated and that the pharmacokinetics of Garenoxacin support once-daily administration.
QbD-Based Development and Validation of Novel Stability-Indicating Method for the Assay and Dissolution of Garenoxacin in Garenoxacin Tablets
J AOAC Int 2022 Mar 15;105(2):370-378.PMID:34894249DOI:10.1093/jaoacint/qsab157.
Background: Garenoxacin mesylate is a novel des-fluoro(6) quinolone, approved and marketed for human use in Japan under the name Geninax. Objective: In this current work, a simple and stability-indicating method for the assay and dissolution of Garenoxacin in Garenoxacin tablets 200 mg was performed. New method developed for the particle size measurement of Garenoxacin mesylate Active Pharmaceutical Ingredient using Malvern 2000. Methods: A quality by design (QbD)-based stability-indicating assay method was developed using 0.1% (v/v) formic acid in water and methanol (70:30). Using a photodiode array detector the peak purity of the Garenoxacin peak for all degradation samples was studied. The biopharmaceutical classification system (BCS) solubility of Garenoxacin mesylate active pharmaceutical ingredient (API) was studied by a modified shake flask method. A dissolution test method was developed using 0.1 N hydrochloric acid as the medium, United State Pharmacopoeia apparatus-II (paddle), revolution per minute (rpm) 50, temperature 37 ± 0.5°C and time 30 min. Liquid paraffin was used as the dispersant in the particle size measurement of Garenoxacin mesylate API using the Malvern Mastersizer-wet method. Results: The QbD-based RP-HPLC method was stability-indicating, simple, precise, and accurate. The assay method was linear over 12.5 to 75 µg/mL at the detection wavelength of 280 nm. A UV-based method was developed and validated for the dissolution of Garenoxacin 200 mg tablets and the method was found to be linear over 2.9 to 34.2 µg/mL at 280 nm. Based on data, the dissolution tolerance for Garenoxacin 200 mg tablets was proposed as Q not less than 80% at time 30 min (% drug released with respect to label claim (Q). The effect of Garenoxacin mesylate API particle size in the tablet dosage form was studied using particles of 92 µm and 220 µm [90% of the total particles are smaller than this size (D90)] and it was found that there was no impact on the in vitro dissolution profile. Conclusion: The reported stability-indicating assay and dissolution test methods can be used in regular QC testing of Garenoxacin 200 mg tablets. The Malvern particle size wet dispersion measurement method developed and validated for Garenoxacin mesylate API is simple and robust. Highlights: A QbD based RP-HPLC method (using Design Expert Software version 11) was developed and studied peak purity of Garenoxacin peak using Photo Diode Array detector (for all degradation samples, control sample and standard solution) and the same method is validated following USP and ICH guidelines. LC-MS compatible volatile buffer solution is used in the preparation of the mobile phase for the novel stability-indicating RP-HPLC assay method.