Methicillin (20 μg/mL, 24 h) causes a sharp decline in S. aureus CFU [2].

Methicillin (40 mg/kg intramuscularly every 6 hours for five days) in S. rabbits infected with SARS[2].

Absorption, Distribution and Excretion
Methicillin is not absorbed after oral administration. It is not administered orally because of its low absorption rate and easy destruction by gastric acid. After intramuscular injection, peak plasma concentrations are reached in approximately 30 minutes to 1 hour. A typical adult dose of 1 gram can result in plasma concentrations exceeding 10 micrograms/mL… …A 2-gram dose can achieve peak plasma concentrations exceeding 20 micrograms/mL, with approximately 8 micrograms/mL remaining after 4 hours. Approximately 40% of methicillin in plasma is bound to proteins. Methicillin does not readily penetrate cerebrospinal fluid; however, higher concentrations of methicillin are observed in the cerebrospinal fluid of patients with meningitis… This drug… is distributed in various body fluids and tissues. Methicillin is excreted unchanged in the urine… Approximately two-thirds of the intramuscular dose is cleared via this route within 4 hours. …In cases of renal failure, methicillin persists in plasma for a longer period at higher concentrations. The portion of injected methicillin that is undetectable in urine is excreted via bile and ultimately eliminated through feces. Recent studies have shown that some drugs can actively cross the human placenta, including methicillin sodium…/Methicillin Sodium/ For more complete data on the absorption, distribution, and excretion of methicillin (21 in total), please visit the HSDB records page. Metabolism/Metabolites Hepatic metabolism (20-40%). Produced as 2,6-dimethoxyphenylpenicillic acid in Bacillus. /Excerpt from Table/ Biological Half-Life 25-60 minutes The half-life of methicillin in the serum of adults with normal renal function is 0.4-0.5 hours. Patients with impaired renal function may have higher serum concentrations of methicillin, and the serum half-life may also be prolonged. The average serum half-life in patients with anuria has been reported to be 4-6 hours. A study of children aged 2-16 years showed that the average serum half-life of methicillin after intravenous injection was 0.8 hours, and after intramuscular injection, it was 1.6 hours. Serum concentrations of methicillin in newborns are generally higher than in older children, and the serum half-life is also longer. The serum half-life of this drug is generally inversely proportional to birth weight, gestational age, and chronological age. It has been reported that the serum half-life of methicillin in newborns with a birth weight less than 2 weeks is 2-3.9 hours, while in newborns with a birth weight greater than 2 weeks, or newborns weighing 2 kg or more and born before 6.5 weeks of age, the serum half-life is 0.9-3.3 hours.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Infants ingest very small amounts of methicillin through breast milk, and no adverse reactions are expected. There are reports that penicillin-type drugs occasionally disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. Methicillin can be used in breastfeeding women.
◉ Effects on Breastfed Infants
No relevant published information was found as of the revision date.
◉ Effects on Lactation and Breast Milk
No relevant published information was found as of the revision date.

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Drug Interactions
Methicillin sodium may have physical and/or chemical incompatibilities with certain drugs, including aminoglycosides and tetracyclines, but compatibility depends on a variety of factors (e.g., drug concentration, specific diluent used, final pH, temperature). /Methicillin Sodium/
In vitro studies have shown that mixing penicillin-type drugs with aminoglycosides results in significant mutual inactivation; if these two classes of antibiotics are used concurrently, they should be administered at different sites at least 1 hour apart. Penicillin-type drugs
Concomitant use of methotrexate with penicillin-type drugs leads to decreased methotrexate clearance and methotrexate toxicity; this is thought to be due to competition for renal tubular secretion; patients should be closely monitored; it may be necessary to increase the dose of leucovorin and prolong the dosing time. Penicillin-type drugs
Since bacteriostatic drugs (chloramphenicol, erythromycin, sulfonamides, or tetracyclines) may interfere with the bactericidal effect of penicillin-type drugs in the treatment of meningitis or other cases requiring rapid bactericidal action, concurrent use is best avoided; however, chloramphenicol and ampicillin are sometimes administered concurrently to pediatric patients. Penicillin-type drugs
For more complete data on drug interactions of methotrexate (7 types), please visit the HSDB record page.

[1]. Sharon S. Castle. Methicillin. xPharm: The Comprehensive Pharmacology Reference 2007, Pages 1-4.

[2]. Treatment of Experimental Staphylococcus aureus Endocarditis: Comparison of Cephalothin, Cefazolin, and Methicillin. Antimicrob Agents Chemother. 1978 Jan; 13(1): 74–77.

Methicillin is a penicillin with the structure 6-aminopenicillanic acid, where one amino hydrogen atom is replaced by a 2,6-dimethoxybenzoyl group. It is an antibacterial drug. It is both a penicillin and a penicillin allergen. It is the conjugate acid of methicillin(1-). Methicillin is one of the few penicillin species resistant to penicillinase but sensitive to penicillin-binding proteins. It is easily inactivated by gastric acid, therefore requiring injection. Methicillin has been reported in Tanacetum argenteum, Streptomyces cavourensis, and several other microorganisms for which relevant data exist. Methicillin is a semi-synthetic, narrow-spectrum, β-lactamase-resistant penicillin antibiotic with bactericidal and β-lactamase-resistant activity. Methicillin binds to specific penicillin-binding proteins (BPB) on the bacterial cell wall, thereby preventing the cross-linking of peptidoglycan, a key component of the bacterial cell wall. This leads to the destruction of the bacterial cell wall, ultimately resulting in bacterial lysis. Methicillin is one of the few penicillins that is resistant to penicillinase but sensitive to penicillin-binding proteins. It is easily inactivated by gastric acid and therefore requires injection. Indications: Used to treat infections caused by susceptible Gram-positive bacteria, particularly those caused by β-lactamase-producing bacteria resistant to most penicillins (such as Staphylococcus aureus). Mechanism of Action: Similar to other β-lactam antibiotics, methicillin works by blocking bacterial cell wall synthesis. Methicillin prevents cross-linking between peptidoglycan polymer chains, a major component of the cell wall of Gram-positive bacteria. Methicillin achieves this by binding to and competitively inhibiting the transpeptidase that produces the peptide (D-alanyl-alanine) used by bacteria in cross-linking peptidoglycan. Penicillins and their metabolites are potent immunogens because they can bind to proteins and act as haptens to trigger an acute antibody-mediated immune response. The most common (approximately 95%) or "major" determinant of penicillin allergy is the penicillin acyl determinant, which arises from the ring-opening of the penicillin β-lactam ring. This allows penicillin to bind to proteins via the amide group. "Minor" determinants (less common) are other metabolites, including native penicillin and penicillinic acid. /Penicillin/
A bactericidal agent; inhibits bacterial cell wall synthesis. Its mechanism of action depends on penicillin's ability to reach and bind to penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (including transpeptidase, carboxypeptidase, and endopeptidase) are enzymes involved in the final stages of bacterial cell wall assembly and in the remodeling of the cell wall during bacterial growth and division. Penicillin binds to and inactivates penicillin-binding proteins, leading to bacterial cell wall fragility and lysis. /Penicillin/

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Therapeutic Uses
Penicillin
Methicillin/used for/treating bone and joint infections caused by susceptible bacteria. /Included on US product label; Not included on Canadian product label/
Methicillin/is used for/the treatment of bacterial endocarditis caused by susceptible bacteria. /Included on US product label; Not included on Canadian product label/
Methicillin/is indicated for/the treatment of bacterial sepsis caused by susceptible bacteria. /Included on US product label/
For more complete data on the therapeutic uses of methicillin (7 types), please visit the HSDB record page.

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Drug Warnings
Methicillin should not be used as a first-line treatment for infections that can be treated with penicillin G.
An important biological effect of penicillin (unrelated to hypersensitivity or "toxicity") is alteration of the bacterial flora at its site of action. /Penicillin/
Intramuscular injection of methicillin is more painful than other penicillins; the need for frequent injections (every 2-3 hours) is a significant drawback for long-term treatment.
In some people…flora changes can lead to infection. Dermatitis primarily affecting the scrotum and groin has been observed… A significant adverse reaction that may occur after penicillin treatment for syphilis is the Jalish-Herxheimer reaction… /Penicillin/
For more complete data on drug warnings for methicillin (21 of them), please visit the HSDB records page.

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Pharmacodynamics
Methicillin (INN, BAN) or methicillin (USAN) is a narrow-spectrum β-lactam penicillin antibiotic. It is no longer used clinically. The role of methicillin in treatment has been largely replaced by flucloxacillin and dicloxacillin, but the term methicillin-resistant Staphylococcus aureus (MRSA) is still used to describe Staphylococcus aureus strains that are resistant to all penicillins.

C17H20N2O6S

380.4155

380.104

61-32-5

Methicillin sodium salt;132-92-3;Methicillin sodium hydrate;7246-14-2

6087

Typically exists as solid at room temperature

1.277

2

7

5

26

600

3

CC1(C(N2C(S1)C(C2=O)NC(=O)C3=C(C=CC=C3OC)OC)C(=O)O)C

RJQXTJLFIWVMTO-TYNCELHUSA-N

InChI=1S/C17H20N2O6S/c1-17(2)12(16(22)23)19-14(21)11(15(19)26-17)18-13(20)10-8(24-3)6-5-7-9(10)25-4/h5-7,11-12,15H,1-4H3,(H,18,20)(H,22,23)/t11-,12+,15-/m1/s1

(2S,5R,6R)-6-[(2,6-dimethoxybenzoyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

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.)