Cell wall synthesis

1. 抗菌活性与协同作用： - 文献[2]通过肉汤稀释法测定氟氯西林对金黄色葡萄球菌的最低抑菌浓度（MIC）为0.25-2 μg/mL。当与阿莫西林联合使用时，对产β-内酰胺酶菌株的协同作用显著，部分抑菌浓度（FIC）指数≤0.5，显示出相加或协同效应 [2]

氟氯西林的血清消除半衰期为1.31-1.39小时，单次250mg剂量给药后6小时，氟氯西林的血清浓度为0.46微克/mL[1]。口服氟氯西林不会影响汗液电解质，也不是汗液检测的禁忌症[2]。据报道，氟氯西林在人体内代谢为青霉唑酸、具有抗菌活性的5''-羟甲基衍生物和5''-羟甲基衍生物的青霉唑酸。氟氯西林在大鼠体内的代谢相似[3]。

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1. 动物模型中的疗效： - 文献[1]在大鼠植入物相关金黄色葡萄球菌感染模型中，比较了氟氯西林（100 mg/kg，每日2次，腹腔注射）与莫西沙星、利福平及联合治疗的效果。结果显示，氟氯西林单药治疗可显著降低植入物周围组织的细菌负荷（p<0.05），但效果弱于利福平联合治疗 [1]
2. 体内协同作用验证： - 文献[2]在小鼠败血症模型中，氟氯西林（50 mg/kg，皮下注射）与阿莫西林（100 mg/kg）联合使用可提高存活率至70%，显著优于单药治疗组（存活率分别为40%和30%） [2]

Animal Model: Male Wistar rats[1]
Dosage: 200 mg/kg
Administration: Intraperitoneal injection; three times/day, for 21 days
Result: Reducted germs in the biofilm and in the bone tissue.

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1. Implant Infection Model (Reference [1]): - Animals: Male Sprague-Dawley rats (250–300 g) - Infection Induction: Polymethyl methacrylate (PMMA) beads contaminated with Staphylococcus aureus (ATCC 25923) were implanted into the femoral medullary cavity - Dosing Regimen: Treatment was initiated 24 hours after infection. flucloxacillin was dissolved in normal saline at a dose of 100 mg/kg, administered via intraperitoneal injection twice daily for 7 days - Evaluation Indicators: After treatment, the animals were euthanized. Tissue surrounding the implant was collected for bacterial counting and histopathological analysis [1]
2. Sepsis Model (Reference [2]): - Animals: Female BALB/c mice (20–25 g) - Infection Induction: Staphylococcus aureus (1×10⁷ CFU/mouse) was injected via the tail vein - Dosing Regimen: Treatment was initiated 1 hour after infection. flucloxacillin was dissolved in sterile water at a dose of 50 mg/kg, administered via subcutaneous injection three times daily for 3 days - Evaluation Indicators: Survival rates were recorded within 7 days, and blood and organs were collected for bacterial culture [2]

Absorption, Distribution and Excretion
Bioavailability is 50–70% following oral administration.

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Metabolism / Metabolites
Hepatic.
Flucloxacillin has known human metabolites that include 6-[[3-(2-Chloro-6-fluorophenyl)-5-(hydroxymethyl)-1,2-oxazole-4-carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid.

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Biological Half-Life
0.75–1 hour

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Floxacillin (flucloxacillin) is not approved for marketing in the United States by the U.S. Food and Drug Administration. It is acceptable to use during breastfeeding and is frequently used abroad to treat mastitis in nursing mothers. Limited information indicates that floxacillin levels in milk are low and are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with penicillins, but these effects have not been adequately evaluated. Floxacillin is acceptable in nursing mothers.
◉ 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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1. Safety Evaluation (Reference [1]): - Rats in the flucloxacillin treatment group showed no significant weight loss or abnormalities in liver and kidney function (serum ALT, AST, and creatinine levels were not significantly different from those in the control group) [1]
2. Tolerance Observation (Reference [2]): - No adverse reactions such as diarrhea, rash, or neurotoxicity were observed in mice receiving flucloxacillin monotherapy or combination therapy [2]

[1]. Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study. Drug Des Devel Ther. 2017 Jun 14;11:1729-1736.

[2]. Antibacterial activity and synergy, in vitro and in vivo, of a combination of amoxycillin and flucloxacillin. Chemotherapy. 1979;25(1):30-9.

Flucloxacillin is a penicillin compound having a 6beta-[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazole-4-carboxamido] side-chain. It has a role as an antibacterial drug. It is a penicillin and a penicillin allergen. It is a conjugate acid of a flucloxacillin(1-).
Antibiotic analog of [cloxacillin].
Flucloxacillin is a narrow-spectrum, semisynthetic isoxazolyl penicillin with antibacterial activity. Floxacillin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This interrupts bacterial cell wall synthesis and results in the weakening of the bacterial cell wall, eventually causing cell lysis.
Antibiotic analog of CLOXACILLIN.

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Drug Indication
Used to treat bacterial infection by susceptible microorganisms.

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Mechanism of Action
By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, flucloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that flucloxacillin interferes with an autolysin inhibitor.

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1. Clinical Application Background: - flucloxacillin is a semisynthetic penicillin-class antibiotic. It exerts bactericidal effects by inhibiting bacterial cell wall synthesis and exhibits high activity against β-lactamase-producing staphylococci and streptococci [1][2]
2. Advantages of Combination Therapy: - Reference [2] points out that the combination of flucloxacillin and amoxicillin can expand the antibacterial spectrum and reduce the selective pressure for drug-resistant mutants, making it particularly suitable for mixed infections or severe infections [2]
3. Limitations: - Reference [1] emphasizes that flucloxacillin is ineffective against methicillin-resistant Staphylococcus aureus (MRSA), and treatment regimens should be selected based on drug susceptibility testing [1]

C19H17N3O5FSCL

453.87178

453.056

C, 50.28; H, 3.78; Cl, 7.81; F, 4.19; N, 9.26; O, 17.63; S, 7.06

5250-39-5

Flucloxacillin sodium;1847-24-1

21319

Solid powder

1.6±0.1 g/cm3

677.3±55.0 °C at 760 mmHg

363.4±31.5 °C

0.0±2.2 mmHg at 25°C

1.672

2.6

138.04

2

8

4

30

758

3

O=C([C@@H](C(C)(C)S[C@]1([H])[C@@H]2NC(C3=C(C)ON=C3C4=C(F)C=CC=C4Cl)=O)N1C2=O)O

UIOFUWFRIANQPC-JKIFEVAISA-N

InChI=1S/C19H17ClFN3O5S/c1-7-10(12(23-29-7)11-8(20)5-4-6-9(11)21)15(25)22-13-16(26)24-14(18(27)28)19(2,3)30-17(13)24/h4-6,13-14,17H,1-3H3,(H,22,25)(H,27,28)/t13-,14+,17-/m1/s1

4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 6-(((3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl)carbonyl)amino)-3,3-dimethyl-7-oxo-, (2S(2alpha,5alpha,6beta))

Floxapen; Flucloxacillin; FLOXACILLIN; 5250-39-5; flucloxacilina; Flucloxacilline; Flucloxacillinum; BRL 2039; 3-(2-Chloro-6-fluorophenyl)-5-methyl-4-isoxazolylpenicillin; BRL 2039; Floxacillin

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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。