For S, cloxacillin (0–2048 µg/mL; 20–24 h) exhibits satisfactory antibacterial action. MIC values for aureus 8325-4 and DU1090 are both 0.125 µg/mL[1]. In vitro, cloxacillin (0.015625 μg/mL; 6 h) suppresses the hemolytic activity of Hlα, and this suppression is enhanced when combined with TZ and TZ. Additionally, cloxacillin inhibits the inflammatory response by preventing the activation of MAPKs, NF-кB, and proteins linked to NLRP3[1].

Mice are protected against S by cloxacillin (1.6125 mg/kg; sc; 12-h intervals for 72 h). When combined with thioridazine and tetracycline, aureus can cause peritonitis in vivo[1]. When combined with anti-IL-15 antibodies, cloxacillin (7.5 mg/per; ip; twice daily starting on day 3) results in less severe synovitis and less bone erosion[3].

Cell Viability Assay[1]
Cell Types: S. aureus 8325-4, S. aureus DU1090 (an Hlα-deleted strain)
Tested Concentrations: 0-2048 µg/mL
Incubation Duration: 20-24 h
Experimental Results: Inhibited S. aureus 8325-4 and DU1090 with MIC values both of 0.125 μg/mL.

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Western Blot Analysis[1]
Cell Types: S. aureus 8325-4
Tested Concentrations: 0.015625 μg/mL (combines with Thioridazine (TZ, 0.25 μg/mL) and Tetracycline (TC, 0.03125 μg/mL)).
Incubation Duration: 6 h
Experimental Results: Inhibited the expression of Hlα and the inhibition was more pronounced when combined with TZ and TC.

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Western Blot Analysis[1]
Cell Types: RAW264.7 cells (exposes to S. aureus 8325-4/DU1090 or pure Hlα)
Tested Concentrations: 0.015625 μg/mL (combines with TZ (0.25 μg/mL) and TC (0.03125 μg/mL)).
Incubation Duration: 6 h
Experimental Results: Inhibited the activation of MAPKs, NF -кB and NLRP3-related proteins thereby inhibiting the inflammatory response when combined with TC and 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.

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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.

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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.

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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.

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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).

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

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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

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

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)