Quinolone

奥泽诺沙星 (OZN) 的 MIC 范围为 0.008 至 4 mg/L，对临床分离的革兰氏阳性微生物表现出强大的抗菌活性。对于 gyrA 和 grlA (parC) 基因有两个、三个或四个突变的 MRSA、MSSA、MSSE 和 MRSE 菌株，奥泽诺沙星表现出良好的活性[1]。 MSSA 和无乳链球菌菌株受 Ozenoxacin 抑制，耐药率分别 >10−10 和 5.3 × 10−10。泽诺沙星对突变株的最大 MIC 值为 8 mg/L[2]。

Absorption, Distribution and Excretion
Four studies were performed in which varying strengths of ozenoxacin cream, up to 2% (twice the concentration of the marketed formulation), were administered to 110 patients. Three of the studies examined systemic absorption in healthy subjects and in subjects having impetigo. The studies were performed with either single or repeated application of up to 1 g ozenoxacin cream to intact or abraded skin (up to 200 cm squared surface area). No systemic absorption was seen in 84 of 86 subjects, and negligible systemic absorption was seen at the level of detection (0.489 ng/mL) in 2 subjects.
Studies regarding elimination and excretion have not yet been investigated in humans due to the negligible systemic absorption observed in clinical studies.
Ozenoxacin undergoes negligible systemic absorption after its topical administration. Subsequently, since negligible systemic absorption of ozenoxacin was observed in clinical studies, tissue distribution has not been investigated in humans either.
Ozenoxacin undergoes negligible systemic absorption after its topical administration.

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Metabolism / Metabolites
Studies have demonstrated that ozenoxacin is not metabolized in the presence of fresh human skin discs and is minimally metabolized in human hepatocytes.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on ozenoxacin cream during breastfeeding. Because ozenoxacin is poorly absorbed after topical application, it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants after maternal application away from the breast. Although quinolones are generally acceptable for systemic use, ozenoxacin should be avoided on the nipple because the infant could ingest the drug via licking.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
The plasma protein binding of [14 C]-ozenoxacin is moderate at ~80-85% and does not appear to be dependent on concentration.

[1]. In vitro activity of Ozenoxacin against quinolone-susceptible and quinolone-resistant gram-positive bacteria. Antimicrob Agents Chemother. 2013 Dec;57(12):6389-92.

[2]. In vitro selection of mutants resistant to ozenoxacin compared with levofloxacin and ciprofloxacin in Gram-positive cocci. J Antimicrob Chemother. 2015 Jan;70(1):57-61.

Ozenoxacin is a member of quinolines.
To date, ozenoxacin has been used in trials studying the treatment of impetigo. As of December 11, 2017 the FDA approved Ferrer Internacional S.A.'s Xepi (ozenoxacin 1%) as a topically applied cream indicated for the treatment of impetigo caused by *Staphylococccus aureus* or *Streptococcus pyogenes* in adult and pediatric patients 2 months of age and older. Despite being a common and highly contagious bacerial skin infection that affects millions of children and adults in the United States each year, ozenoxacin cream is a novel, non-fluorinated quinolone that has demonstrated safe and effective therapy in both the adult and pediatric population.
Ozenoxacin is a Quinolone Antimicrobial.

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Drug Indication
Ozenoxacin cream is indicated for the topical treatment of impetigo caused by *Staphylococcus aureus* or *Streptococcus pyogenes* in patients aged 2 months of age and older.
FDA Label
Treatment of impetigo

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Mechanism of Action
Ozenoxacin is a quinolone antibiotic drug. And, like most quinolones, ozenoxacin predominately executes its mechanism of action by entering into bacterial cells and acting to inhibit the bacterial DNA replication enzymes DNA gyrase A and topoisomerase IV. As DNA gyrase A and topoisomerase IV are essential to bacterial DNA replication activities including supercoiling, supercoil relaxation, chromosomal condensation, chromosomal decatenation and more, their inhibition is the principal action of ozenoxacin's mechanism and it has been demonstrated to be bactericidal against *S. aureus* and *S. pyogenes* organisms.

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Pharmacodynamics
Although the exposure response relationship for ozenoxacin after it has been applied topically has not yet been studied, a formal relationship is unlikely because systemic exposure of ozenoxacin following its topical application has been measured to be negligible.

C21H21N3O3

363.42

363.158

C, 69.41; H, 5.82; N, 11.56; O, 13.21

245765-41-7

Ozenoxacin-d3

9863827

Solid powder

1.4±0.1 g/cm3

573.5±50.0 °C at 760 mmHg

300.7±30.1 °C

0.0±1.7 mmHg at 25°C

1.694

3.41

87.45

2

6

4

27

645

0

O=C(C1=CN(C2CC2)C3=C(C=CC(C4=CC(C)=C(NC)N=C4)=C3C)C1=O)O

XPIJWUTXQAGSLK-UHFFFAOYSA-N

InChI=1S/C21H21N3O3/c1-11-8-13(9-23-20(11)22-3)15-6-7-16-18(12(15)2)24(14-4-5-14)10-17(19(16)25)21(26)27/h6-10,14H,4-5H2,1-3H3,(H,22,23)(H,26,27)

1-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

GF-001001-00; M 5120; GF-001001-00; M-5120; M-5120; GF001001-00; M5120; GF-001001 00; T-3912; GF-00100100; Ozenoxacin; trade name: Xepi

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 2.86 ~5 mg/mL (7.87~ 13.75 mM )

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。