对于 S，氯唑西林（0–2048 µg/mL；20–24 小时）表现出令人满意的抗菌作用。金黄色葡萄球菌 8325-4 和 DU1090 的 MIC 值均为 0.125 µg/mL[1]。在体外，氯唑西林（0.015625 μg/mL；6 小时）可抑制 Hlα 的溶血活性，且与 TZ 和 TZ 联合使用时，这种抑制作用会增强。此外，氯唑西林通过阻止 MAPK、NF-кB 和 NLRP3 相关蛋白的激活来抑制炎症反应[1]。

氯唑西林（1.6125 mg/kg；皮下注射；间隔 12 小时，持续 72 小时）可保护小鼠免受 S 的侵害。与硫利达嗪、四环素等合用时，可引起体内金黄色葡萄球菌引起腹膜炎[1]。当与抗 IL-15 抗体联合使用时，氯唑西林（7.5 mg/次；腹腔注射；从第 3 天开始每天两次）可减轻滑膜炎的严重程度并减少骨侵蚀[3]。

细胞活力测定[1]
细胞类型：金黄色葡萄球菌 8325-4、金黄色葡萄球菌 DU1090（Hlα 删除菌株）
测试浓度： 0-2048 µg/mL
孵育时间： 20-24 小时
实验结果： 抑制金黄色葡萄球菌 8325-4 和 DU1090，MIC 值均为0.125微克/毫升。

---

蛋白质印迹分析[1]
细胞类型： S. aureus 8325-4
测试浓度： 0.015625 µg/mL（结合与硫利达嗪（TZ，0.25 μg/mL）和四环素（TC，0.03125 μg/mL））。
孵育时间： 6 h
实验结果：抑制Hlα的表达，与TZ、TC联合使用抑制作用更明显。

---

蛋白质印迹分析[1]
细胞类型： RAW264.7 细胞（暴露于金黄色葡萄球菌 8325-4/DU1090 或纯 Hlα）
测试浓度：0.015625 μg/mL（与 TZ (0.25 μg/mL) 和 TC (0.03125 μg/mL) 组合）。
孵育时间： 6 小时
实验结果： 抑制 MAPKs、NF-кB 和 NLRP3 相关蛋白的激活，从而抑制炎症反应。 TC 和 TZ。

Animal/Disease Models: Female balb/c (Bagg ALBino) mouse (6weeks old; peritonitis model)[1].
Doses: 1.6125 mg/kg (combines with TC (3.125 mg/kg) and TZ (25 mg/kg))
Route of Administration: subcutaneous (sc) injection; 12-h intervals for 72 h.
Experimental Results: decreased the degree of inflammatory cell infiltration in the mouse lung tissue and alveolar structures tended to be normal. Dramatically decreased the pathological changes in spleen and liver tissue, as well as diminished the CFU counts of S. aureus in the peritoneal cavity.

---

Animal/Disease Models: Female wildtype C57BL/6 mice (8weeks old; systemic S. aureus-induced arthritis model)
Doses: 7.5 mg/per (combines with 25 µg/per anti-IL-15 antibodies)
Route of Administration: intraperitoneal (ip)injection; twice (two times) daily from day 3 (after bacterial inoculation) and stopped at day 6.
Experimental Results: demonstrated activities of reducing severe synovitis and bone erosions when combined with anti-IL-15 antibodies.

Absorption, Distribution and Excretion
Well absorbed from the gastrointestinal tract.
.../ANTIMICROBIAL AGENTS/ ARE RAPIDLY BUT INCOMPLETELY (30-80%) ABSORBED FROM GI TRACT. ABSORPTION OF DRUGS IS MORE EFFICIENT WHEN THEY ARE TAKEN ON AN EMPTY STOMACH. PEAK PLASMA CONCN ARE ATTAINED BY 1 HR & APPROX 5-10 UG/ML AFTER INGESTION OF 1 G OF OXACILLIN, & SIMILAR VALUES ARE OBTAINED WITH CLOXACILLIN.
SINCE ABSORPTION IS LESS THAN COMPLETE, HIGHER PLASMA CONCN ARE ACHIEVED FOLLOWING IM INJECTION, & LARGER QUANTITIES OF DRUGS ARE RECOVERABLE IN URINE. ...BOUND TO PLASMA ALBUMIN TO GREAT EXTENT (APPROX 90-95%); NONE IS REMOVED FROM CIRCULATION TO SIGNIFICANT DEGREE BY HEMODIALYSIS.
NORMALLY, ABOUT ONE HALF OF.../DRUG/ IS EXCRETED IN URINE IN FIRST 6 HR AFTER CONVENTIONAL ORAL DOSE. THERE IS ALSO SIGNIFICANT HEPATIC ELIMINATION...IN BILE.
ISOXAZOLYL PENICILLINS ARE RAPIDLY EXCRETED BY KIDNEY, & CONCURRENT ADMIN OF PROBENECID RESULTS IN HIGHER & MORE PERSISTENT PLASMA CONCN. /PENICILLINS/
For more Absorption, Distribution and Excretion (Complete) data for CLOXACILLIN (16 total), please visit the HSDB record page.

---

Metabolism / Metabolites
Cloxacillin, like other penicillins, appears to be metabolized via breakage of the beta-lactam ring to form an inactive penicilloic acid metabolite.
PENICILLIN CAN UNDERGO SLOW CONVERSION IN VIVO TO INTERMEDIATES, SUCH AS PENICILLENIC ACID, WHICH CAN REACT WITH APPROPRIATE CONSTITUENTS OF TISSUES. /PENICILLINS/
Cloxacillin is partially metabolized to active and inactive metabolites. In one study following administration of a single 500-mg oral cloxacillin dose, 22% of the absorbed dose was hydrolyzed to penicilloic acids which are microbiologically inactive. Cloxacillin is also hydroxylated to a small extent to a microbiologically active metabolite which appears to be as active as cloxacillin.

---

Biological Half-Life
HALF-LIVES...BETWEEN 30 AND 60 MINUTES.
IN CHILDREN BEING TREATED FOR STAPHYLOCOCCAL INFECTIONS, MEAN ELIMINATION HALF-LIFE WAS 71 MIN.
The serum half-life of cloxacillin in adults with normal renal function is 0.4-0.8 hr.
The serum half-life of cloxacillin is slightly prolonged in patients with impaired renal function and has been reported to range from 0.8-2.3 hr in patients with severe renal impairment.
In one study in children 1 week to 2 years of age, the serum elimination half-life of cloxacillin was 0.8-1.5 hr. Serum concentrations of cloxacillin are generally higher and the serum half-life more prolonged in neonates than in older children.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that cloxacillin produces low levels in milk that 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. Cloxacillin is acceptable in nursing mothers.
◉ Effects in Breastfed Infants
In a telephone follow-up study, 10 nursing mothers reported taking cloxacillin (dosage unspecified). Two mothers reported diarrhea in their infants. No rashes or candidiasis were reported among the exposed infants.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

---

Protein Binding
Cloxacillin is approximately 94% protein-bound in plasma, primarily to albumin.

[1]. The combination of cloxacillin, thioridazine and tetracycline protects mice against Staphylococcus aureus peritonitis by inhibiting α-Hemolysin-induced MAPK/NF-κB/NLRP3 activation. Int J Biol Macromol. 2022 Feb 15;198:1-10.

[2]. Antibiotics with Interleukin-15 Inhibition Reduce Joint Inflammation and Bone Erosions but Not Cartilage Destruction in Staphylococcus aureus-Induced Arthritis. Infect Immun. 2018 Apr 23;86(5):e00960-17.

[3]. Group 1 beta-lactamases of Aeromonas caviae and their resistance to beta-lactam antibiotics. Can J Microbiol. 2003 Mar;49(3):207-15.

Cloxacillin is a semisynthetic penicillin antibiotic carrying a 3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamido group at position 6. It has a role as an antibacterial agent and an antibacterial drug. It is a semisynthetic derivative, a penicillin allergen and a penicillin. It is functionally related to an oxacillin. It is a conjugate acid of a cloxacillin(1-).
A semi-synthetic penicillin antibiotic which is a chlorinated derivative of [oxacillin].
Cloxacillin has been reported in Apis cerana with data available.
Cloxacillin Sodium is the sodium salt of cloxaclliin, a semisynthetic beta-lactamase resistant penicillin antibiotic with antibacterial activity. Cloxacillin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall, thereby preventing the cross-linkage of peptidoglycans, which are critical components of the bacterial cell wall. This leads to an interruption of the bacterial cell wall and causes bacterial cell lysis.
Cloxacillin is a semisynthetic beta-lactamase resistant penicillin antibiotic with antibacterial activity. Cloxacillin binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall, thereby preventing the cross-linkage of peptidoglycans, which are critical components of the bacterial cell wall. This leads to an interruption of the bacterial cell wall and causes bacterial cell lysis.
A semi-synthetic antibiotic that is a chlorinated derivative of OXACILLIN.
See also: Cloxacillin Sodium (has salt form); Cloxacillin Benzathine (has salt form).

---

Drug Indication
Cloxacillin is indicated for the treatment of beta-hemolytic streptococcal, pneumococcal, and staphylococcal infections (including beta-lactamase producing organisms).

---

Mechanism of Action
By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, cloxacillin 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 cloxacillin interferes with an autolysin inhibitor.
...ITS ANTIBACTERIAL SPECTRUM AGAINST GRAM-POSITIVE BACTERIA IS LIKE THAT OF PENICILLIN EXCEPT IT IS BROADER BY MARGIN OF THOSE STRAINS OR SPECIES THAT PRODUCE PENICILLINASE. ...IT IS LESS ACTIVE THAN PENICILLIN G AGAINST NON-PENICILLINASE-PRODUCING BACTERIA, ESPECIALLY STREPTOCOCCI. /CLOXACILLIN MONOHYDRATE/
SINCE PENICILLIN HAS NO EFFECT ON EXISTING CELL WALLS, BACTERIA MUST BE MULTIPLYING FOR BACTERIAL ACTION OF PENICILLIN TO BE MANIFEST. /PENICILLINS/
The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/
Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin-binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/
TOLERANCE DEVELOPED TO MULTIPLE DOSING. /PENICILLINS/

C19H18CLN3O5S

435.88

435.065

61-72-3

Cloxacillin sodium monohydrate;7081-44-9;Cloxacillin sodium;642-78-4

6098

Typically exists as solid at room temperature

1.6±0.1 g/cm3

689.7±55.0 °C at 760 mmHg

370.9±31.5 °C

0.0±2.3 mmHg at 25°C

1.685

2.53

138.04

2

7

4

29

722

3

ClC1=CC=CC=C1C1=NOC(C)=C1C(N[C@@H]1C(=O)N2[C@H](C(S[C@]12[H])(C)C)C(=O)O)=O

LQOLIRLGBULYKD-JKIFEVAISA-N

InChI=1S/C19H18ClN3O5S/c1-8-11(12(22-28-8)9-6-4-5-7-10(9)20)15(24)21-13-16(25)23-14(18(26)27)19(2,3)29-17(13)23/h4-7,13-14,17H,1-3H3,(H,21,24)(H,26,27)/t13-,14+,17-/m1/s1

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

HSDB-3042Cloxacillin HSDB3042 HSDB 3042

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。

---

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。

View More

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)

---

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。

View More

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

---

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。

---

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。