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
Not absorbed following oral administration.
METHICILLIN IS NOT EMPLOYED BY ORAL ROUTE BECAUSE IT IS POORLY ABSORBED & READILY DESTROYED BY ACIDIC GASTRIC CONTENTS. WHEN DRUG IS GIVEN IM, PEAK PLASMA CONCN ARE REACHED IN ABOUT 30 MIN-1 HR. AFTER CONVENTIONAL DOSE OF 1 G IN ADULTS, PLASMA CONCN IN EXCESS OF 10 UG/ML ARE DEMONSTRABLE...
...2-G DOSE PROVIDES PEAK CONCN OVER 20 UG/ML, & APPROX 8 UG/ML IS STILL PRESENT AFTER 4 HR. ABOUT 40% OF METHICILLIN IN PLASMA IS BOUND TO PROTEIN. METHICILLIN DOES NOT READILY PENETRATE INTO CSF; HOWEVER, SIGNIFICANT CONCN ARE PRESENT IN PATIENTS WITH MENINGITIS... DRUG...WELL DISTRIBUTED IN VARIOUS BODY FLUIDS & TISSUES.
METHICILLIN IS EXCRETED UNCHANGED IN URINE...ABOUT 2/3 OF IM DOSE IS ELIMINATED BY THIS ROUTE IN 4 HR. ... METHICILLIN PERSISTS FOR LONG PERIOD & @ HIGH CONCN IN PLASMA IN CASES OF RENAL FAILURE. ... PORTION OF INJECTED METHICILLIN THAT CANNOT BE DETECTED IN URINE IS EXCRETED INTO BILE & IS ELIMINATED BY WAY OF FECES.
DRUGS RECENTLY SHOWN TO ACTIVELY CROSS HUMAN PLACENTA INCL...SODIUM METHICILLIN... /METHICILLIN SODIUM/
For more Absorption, Distribution and Excretion (Complete) data for METHICILLIN (21 total), please visit the HSDB record page.

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Metabolism / Metabolites
Hepatic (20-40%).
YIELDS 2,6-DIMETHOXYPHENYLPENICILLOIC ACID IN BACILLUS. /FROM TABLE/

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Biological Half-Life
25-60 minutes
The serum half-life of methicillin in adults with normal renal function is 0.4-0.5 hours.
Serum concn of methicillin may be higher and the serum half-life prolonged in patients with impaired renal function. The serum half-life of the drug reportedly averages 4-6 hr in anuric patients.
In one study in children 2-16 yr of age, the serum half-life of methicillin averaged 0.8 hr after IV administration and 1.6 hr after IM administration. Serum concn of methicillin are generally higher and the serum half-life is longer in neonates than in older children. The serum half-life of the drug is generally inversely proportional to birthweight, gestational age, and chronologic age. The serum half-life of methicillin reportedly ranges from 2-3.9 hr in low birthweight neonates 2 wk of age or younger and ranges from 0.9-3.3 hr in low birthweight neonates older than 2 wk of age or neonates weighing 2 kg or more who are 6.5 wk of age or younger.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Amounts of methicillin ingested by the infant in breastmilk are small and would not be expected to cause any adverse effects. 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. Methicillin 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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Interactions
Methicillin sodium is potentially physically and/or chemically incompatible with some drugs, including aminoglycosides and tetracyclines, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature). /Methicillin sodium/
Mixing penicillins with aminoglycosides in vitro has resulted in substantial mutual inactivation; if these groups of antibacterials are to be administered concurrently, they should be administered at separate sites at least 1 hour apart. /Penicillins/
Concurrent of /methotrexate/ with penicillins has resulted in decreased clearance of methotrexate and in methotrexate toxicity; this is thought to be due to competition for renal tubular secretion; patients should be closely monitored; leucovorin doses may need to be increased and administered for longer periods of time. /Penicillins/
Since bacteriostatic drugs /Chloramphenicol, erythromycins, sulfonamides, or tetracyclines/ may interfere with the bactericidal effect of penicillins in the treatment of meningitis or in other situations in which a rapid bactericidal effect is necessary, it is best to avoid concurrent therapy; however, chloramphenicol and ampicillin are sometimes administered concurrently to pediatric patients. /Penicillins/
For more Interactions (Complete) data for METHICILLIN (7 total), 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 that is 6-aminopenicillanic acid in which one of the amino hydrogens is replaced by a 2,6-dimethoxybenzoyl group. It has a role as an antibacterial drug. It is a penicillin and a penicillin allergen. It is a conjugate acid of a methicillin(1-).
One of the penicillins which is resistant to penicillinase but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection.
Methicillin has been reported in Tanacetum argenteum, Streptomyces cavourensis, and other organisms with data available.
Methicillin is a semisynthetic, narrow spectrum beta-lactamase-resistant penicillin antibiotic with bactericidal and beta-lactamase resistant activity. Methicillin binds to specific penicillin-binding proteins (BPBs) on 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 lysis.
One of the PENICILLINS which is resistant to PENICILLINASE but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection.

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Drug Indication
Used to treat infections caused by susceptible Gram-positive bacteria, particularly beta-lactamase-producing organisms such as Staphylococcus aureus that would otherwise be resistant to most penicillins.

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Mechanism of Action
Similar to other beta-lactam antimicrobials, meticillin blocks synthesis of the bacterial cell wall. Meticillin stops cross-linkage between the peptidoglycan polymer chains, which make up a large portion of gram-positive bacterial cell walls. It does this by binding to and competitively inhibiting the transpeptidase enzyme used by bacteria to cross-link the peptide (D-alanyl-alanine) used in peptidogylcan synthesis.
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/

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Therapeutic Uses
Penicillins
Methicillin /is/ indicated in the treatment of bone and joint infections caused by susceptible organisms. /Included in US product labeling; Not included in Canadian product labeling/
Methicillin /is/ indicated in the treatment of bacterial endocarditis caused by susceptible organisms. /Included in US product labeling; Not included in Canadian product labeling/
Methicillin /is/ indicated in the treatment of bacterial septicemia caused by susceptible organisms. /Included in US product labeling/
For more Therapeutic Uses (Complete) data for METHICILLIN (7 total), please visit the HSDB record page.

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Drug Warnings
METHICILLIN MUST NOT BE USED IN PREFERENCE TO PENICILLIN G IN INFECTIONS AMENDABLE TO TREATMENT WITH LATTER DRUG.
IMPORTANT BIOLOGICAL EFFECT OF PENICILLIN, UNRELATED TO HYPERSENSITIVITY OR TO "TOXIC" REACTION, IS ALTERATION OF BACTERIAL FLORA IN AREAS OF BODY TO WHICH IT GAINS ACCESS. /PENICILLIN/
IM INJECTION OF METHICILLIN IS MORE PAINFUL THAN IS CASE FOR OTHER PENICILLINS; NEED FOR FREQUENT INJECTIONS (EVERY 2-3 HR) IS DEFINITE DISADVANTAGE WHEN PROLONGED THERAPY BY THIS ROUTE IS REQUIRED.
IN SOME PERSONS...SUPRAINFECTION RESULTS FROM CHANGES IN FLORA. DERMATITIS INVOLVING PRIMARILY SCROTAL & INGUINAL SKIN...HAS BEEN OBSERVED... DRAMATIC EFFECT THAT MAY FOLLOW USE OF PENICILLIN IN SYPHILIS IS JARISCH-HERXHEIMER REACTION... /PENICILLINS/
For more Drug Warnings (Complete) data for METHICILLIN (21 total), please visit the HSDB record page.

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Pharmacodynamics
Meticillin (INN, BAN) or methicillin (USAN) is a narrow spectrum beta-lactam antibiotic of the penicillin class. It is no longer clinically used. Its role in therapy has been largely replaced by flucloxacillin and dicloxacillin, however the term methicillin-resistant Staphylococcus aureus (MRSA) continues to be used to describe Staphylococcus aureus strains 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.)