Sparfloxacin (CI-978; AT-4140)   中文名称: 司帕沙星

抗生素司帕沙星 (CI-978) 具有强大而广泛的抗菌作用。 90% 的测试菌株对革兰氏阳性菌（包括链球菌、肠球菌和葡萄球菌属）的最低抑菌浓度 (MIC) 范围为 0.1 至 0.78 μg/ml，对革兰氏阳性菌的 MIC 范围为 0.1 至 0.78 μg/ml。阴性细菌，包括葡萄球菌属。假单胞菌属和肠杆菌科含有 0.0125 至 1.56 μg/ml。其最低抑菌浓度（MIC）范围为：对非葡萄糖发酵菌为0.025至0.78μg/ml，对厌氧菌为0.2至0.78μg/ml，对军团菌为0.0125至0.05μg/ml。在小鼠中，口服司帕沙星 (CI-978) 可有效治疗由金黄色葡萄球菌、化脓性链球菌、肺炎链球菌、大肠杆菌和铜绿假单胞菌引起的全身感染[1]。 DNA 合成受到司帕沙星的抑制，其靶标为 DNA 旋转酶 [2]。

Absorption, Distribution and Excretion
Absorbed well after oral administration, with an absolute oral bioavailability of 92%. Co-administration with milk or food does not affect its absorption; however, concurrent use with antacids containing magnesium hydroxide and aluminum hydroxide can reduce the oral bioavailability of sparfloxacin by up to 50%. Metabolism/Metabolites Hepatic metabolism. Primarily metabolized to glucuronide conjugates via phase II glucuronidation. Metabolism does not utilize or interferes with the cytochrome P450 enzyme system. Biological Half-Life Mean terminal elimination half-life is 20 hours (range 16-30 hours). The half-life is prolonged in patients with renal impairment (creatinine clearance < 50 mL/min).

Use of Sparfloxacin during Pregnancy and Lactation ◉ Overview of Use During Lactation There is currently no information regarding the use of sparfloxacin during lactation. Traditionally, fluoroquinolones are not recommended for use in infants due to concerns about adverse effects on the developing joints of infants. However, recent studies suggest the risk is minimal. Calcium in breast milk may prevent the absorption of small amounts of fluoroquinolones in breast milk, but there is currently insufficient data to confirm or refute this claim. Lactating women can use sparfloxacin, but close monitoring of the infant's gut microbiota is necessary, for example, for changes in diarrhea or candidiasis (thrush, diaper rash). However, alternative medications with available safety information are preferred. ◉ Effects on Breastfed Infants No published information was found as of the revision date. ◉ Effects on Lactation and Breast Milk No published information was found as of the revision date.

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Protein Binding Serum plasma protein binding is low, approximately 45%.

[1]. In vitro and in vivo antibacterial activities of AT-4140, a new broad-spectrum quinolone. Antimicrob Agents Chemother, 1989. 33(8): p. 1167-73.

[2]. Pan, X.S. and L.M. Fisher, Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective targeting of gyrase or topoisomerase IV by quinolones. Antimicrob Agents Chemother, 1997. 41(2): p. 471-4.

Sparfloxacin is a quinolone antibiotic, belonging to the quinolone monocarboxylic acid class, N-arylpiperazine class, quinolone antibiotics, and fluoroquinolone antibiotics. Sparfloxacin is a fluoroquinolone antibiotic used to treat bacterial infections. It exerts its antibacterial activity by inhibiting bacterial topoisomerase DNA gyrase. DNA gyrase is an important enzyme that controls DNA topology and assists in DNA replication, repair, inactivation, and transcription. Sparfloxacin is a fluoroquinolone antibiotic that inhibits DNA replication and transcription by inhibiting bacterial DNA gyrase. Due to its high rate of phototoxicity, sparfloxacin has been withdrawn from the US market. Drug Indications This drug is indicated for the treatment of the following adult infections caused by susceptible strains of microorganisms: community-acquired pneumonia (caused by Chlamydia pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, or Streptococcus pneumoniae) and acute bacterial exacerbations of chronic bronchitis (caused by Chlamydia pneumoniae, Enterobacter cloacae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Staphylococcus aureus, or Streptococcus pneumoniae). FDA Label Mechanism of Action Sparfloxacin's bactericidal action derives from the inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV, two enzymes essential for bacterial DNA replication, transcription, repair, and recombination. Pharmacodynamics Sparfloxacin is a synthetic broad-spectrum fluoroquinolone antibacterial drug, belonging to the same class as ofloxacin and norfloxacin. Sparfloxacin exhibits in vitro activity against a variety of Gram-negative and Gram-positive bacteria. Sparfloxacin exerts its antibacterial effect by inhibiting the bacterial topoisomerase DNA gyrase. DNA gyrase is an important enzyme that controls DNA topology and assists in DNA replication, repair, inactivation, and transcription. Quinolones have different chemical structures and mechanisms of action than β-lactam antibiotics. Therefore, quinolones may be effective against bacteria resistant to β-lactam antibiotics. Although cross-resistance between sparfloxacin and other fluoroquinolones has been observed, some microorganisms resistant to other fluoroquinolones may be sensitive to sparfloxacin. In vitro studies have shown that sparfloxacin, in combination with rifampin, has antagonistic effects against Staphylococcus aureus.

C19H22F2N4O3

392.3998

392.165

110871-86-8

60464

Light yellow to yellow solid powder

1.4±0.1 g/cm3

640.4±55.0 °C at 760 mmHg

265°C

341.1±31.5 °C

0.0±2.0 mmHg at 25°C

1.627

1.2

100.59

3

9

3

28

691

2

C[C@@H]1CN(C[C@@H](N1)C)C2=C(C(=C3C(=C2F)N(C=C(C3=O)C(=O)O)C4CC4)N)F

DZZWHBIBMUVIIW-DTORHVGOSA-N

InChI=1S/C19H22F2N4O3/c1-8-5-24(6-9(2)23-8)17-13(20)15(22)12-16(14(17)21)25(10-3-4-10)7-11(18(12)26)19(27)28/h7-10,23H,3-6,22H2,1-2H3,(H,27,28)/t8-,9+

5-amino-1-cyclopropyl-7-((3S,5R)-3,5-dimethylpiperazin-1-yl)-6,8-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

CI 978 CI-978 CI978 Sparfloxacin Esparfloxacino Zagam

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 本产品在运输和储存过程中需避光。

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

0.1 M NaOH : ~50 mg/mL (~127.42 mM)
DMSO : ~3.33 mg/mL (~8.49 mM)
H2O : ~0.67 mg/mL (~1.71 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。