At a minimum inhibitory concentration (MIC) of 0.5 μg against the Xen strain of Staphylococcus aureus, mice treated with naprocillin (100 mg/kg; sc) showed bactericidal activity against both methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA)[3].

Absorption, Distribution and Excretion
Following intravenous injection of 500 mg nafcillin, the average plasma concentration is approximately 30 µg/mL. This concentration is reached within 5 minutes of injection. Nafcillin is primarily eliminated via non-renal routes, namely hepatic inactivation and bile excretion. Nafcillin has been reported to be widely distributed in various body fluids, including bile, pleural effusion, amniotic fluid, and synovial fluid. …Oral absorption is irregular…regardless of whether it is taken with food or on an empty stomach. Following parenteral administration, nafcillin plasma concentrations are lower than…the equivalent dose of oxacillin. This is related to the increased apparent volume of distribution of nafcillin, due to its selective isolation in the liver and other tissues. Nafcillin is approximately 90% bound to plasma proteins, and only about 10% of the oral dose is recovered in the urine. Probenecid further reduces urinary excretion. The primary route of excretion is bile, with approximately 90% of a single intravenous dose excreted via bile. Some of the drug is reabsorbed in the small intestine. Peak concentrations of nafcillin in bile are significantly higher than in plasma. After oral administration of 1 gram of nafcillin sodium, a plasma concentration of 0.7 mg/dL is achieved within 1 hour; after intramuscular injection of 0.5 gram, a plasma concentration of 0.6 mg/dL is achieved within 1 hour. 17% of the oral dose is excreted in the urine; 36% of the intramuscular dose is excreted in the urine. /Nafcillin Sodium/ For more complete data on the absorption, distribution, and excretion of nafcillin (19 types), please visit the HSDB record page.

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Metabolism/Metabolites
In the biotransformation of most penicillins, hepatic metabolism accounts for less than 30%. …The proton-catalyzed hydrolysis of penicillin to penicillic acid is well documented… This process is catalyzed by bacterial β-lactamases and mammalian enzymes. /Penicillin/
Nafcillin is converted to 2-ethoxy-1-naphthamidopenicillic acid in Bacillus subtilis. /Table Data/
Approximately 60% of nafcillin doses are metabolized in the liver to inactive metabolites.

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Biological Half-Life
Three independent studies determined that the serum half-life of intravenously administered nafcillin ranged from 33 to 61 minutes.
The normal half-life of nafcillin is 0.5 hours. /Table Data/
In adults with normal renal and hepatic function, the average serum half-life of nafcillin is 0.5–1.5 hours. In a study of healthy adults, the distribution half-life of nafcillin was 0.17 hours, and the elimination half-life was 1.02 hours.
According to reports, the serum half-life of nafcillin is 1.2–1.9 hours in patients with creatinine clearance of 3–59 ml/min/1.73 m², and 1.8–2.8 hours in patients with creatinine clearance less than 3 ml/min/1.73 m².
In a study of patients with cirrhosis or extrahepatic biliary obstruction, the mean t1/2α of nafcillin was 0.26 hours and 0.29 hours, respectively, and the mean t1/2β was 1.2 hours and 1.7 hours, respectively. The serum clearance of the drug in these patients was lower than that in patients with normal renal and hepatic function; the mean clearance was 291.5 ml/min in patients with cirrhosis and 163.4 ml/min in patients with extrahepatic obstruction.
In children aged 1 month to 14 years, the serum half-life of nafcillin is 0.75–1.9 hours. Newborns typically have higher serum concentrations of nafcillin than older children, and the serum half-life is also longer. One study showed that the serum half-life of nafcillin in newborns aged 3 weeks and under was 2.2–5.5 hours, while that in newborns aged 4–9 weeks was 1.2–2.3 hours.

Hepatotoxicity
Elevated serum transaminases during high-dose intravenous oxacillin treatment do not appear to occur during high-dose nafcillin treatment. For patients experiencing elevated serum transaminases during high-dose oxacillin treatment, it is safe to switch to intravenous nafcillin or other penicillin antibiotics. Only a very small number of clinically significant cases of hepatotoxicity are associated with nafcillin use. Typically, this injury presents as cholestatic hepatitis, appearing 1 to 6 weeks after initiation of nafcillin, with a potentially long course but eventually resolving. Rash, fever, and eosinophilia are uncommon but can occur (Case 1). This injury is similar to that caused by flucloxacillin and cloxacillin, but much less common with nafcillin. Autoantibodies are uncommon. Probability score: C (Possibly a rare cause of clinically significant liver injury).

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Effects during pregnancy and lactation
◉ Overview of medication use during lactation
While there is currently no information on the use of nafcillin during lactation, it is generally believed that penicillin-type drugs do not have adverse effects on breastfed infants. 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. Nafcillin can be used in breastfeeding women.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on lactation and breast milk
No published information found as of the revision date.

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Protein binding
Nafcillin binds to serum proteins at a rate of 89.9 ± 1.5%, primarily albumin.

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Interactions
When nafcillin is taken concurrently with aspirin, its serum binding rate decreases.
Chloramphenicol may antagonize the effects of penicillin. Penicillin Classes
Theoretically, all penicillin and erythromycin classes may exhibit synergistic antibacterial activity.
Tetracyclines may antagonize the bactericidal effect of penicillins. Antagonistic interactions may exist among all penicillin classes.
For more complete data on interactions of nalidixic acids (14 in total), please visit the HSDB record page.

[1]. Identification of the site of covalent attachment of nafcillin, a reversible suicide inhibitor of beta-lactamase. Biochem J, 1992. 281 ( Pt 1): p. 191-6.

[2]. Bacterial wound colonization after broad-spectrum versus narrow-spectrum antibiotics. Ann Thorac Surg, 1995. 59(3): p. 626-31.

[3]. Rapid Bactericidal Activity of Daptomycin against Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Peritonitis in Mice as Measured with Bioluminescent Bacteria. Antimicrob Agents Chemother. 2007 May; 51(5): 1787-1794.

[4]. Nafcillin enhances innate immune-mediated killing of methicillin-resistant Staphylococcus aureus. J Mol Med (Berl). 2014 Feb;92(2):139-49.

Nafcillin is a penicillin with a (2-ethoxy-1-naphthoyl)amino group at the 6-position of its penicillin ring. It is an antibacterial drug. It is both a penicillin and a penicillin allergen. It is the conjugate acid of nafcillin (1-). Nafcillin is a penicillin-associated semi-synthetic antibiotic belonging to the narrow-spectrum β-lactam antibiotics. It is a β-lactamase-resistant penicillin suitable for treating staphylococcal infections caused by strains resistant to other penicillins (excluding methicillin-resistant Staphylococcus aureus [MRSA]). It can be used as a first-line treatment for methicillin-sensitive Staphylococcus aureus infections. Nafcillin is a penicillin antibiotic. Nafcillin is an injectable second-generation penicillinase-resistant penicillin antibiotic, primarily used to treat moderate to severe staphylococcal infections. Nafcillin is associated with rare, clinically significant specific liver injury. Nafcillin is a semi-synthetic naphthalene and β-lactam antibiotic with antibacterial activity. Nafcillin inhibits bacterial cell wall synthesis through a mechanism similar to penicillin. Penicillinase-resistant nafcillin is used to treat infections caused by penicillin-resistant Staphylococcus strains. (NCI04) A penicillin-associated semi-synthetic antibiotic. See also: Nafcillin sodium (in salt form). Indications: For the treatment of infections caused by penicillinase-producing Staphylococcus aureus that are sensitive to this drug. FDA label. Mechanism of Action: Like other penicillins, nafcillin exerts its bactericidal effect on penicillin-sensitive microorganisms during the active proliferative phase of bacterial cell wall synthesis. It inhibits bacterial cell wall biosynthesis by forming a covalent bond with penicillin-binding proteins that play a key role in the final transpeptidation process. Binding to penicillin-binding proteins inhibits the transpeptidase and carboxypeptidase activities conferred by these proteins, thereby preventing cross-linking.
Naproxil sodium and methicillin are classic examples of structural designs that utilize steric hindrance to inhibit β-lactam hydrolysis. /Naproxil sodium/
Penicillin and its metabolites are potent immunogens because they can bind to proteins and act as haptens to trigger acute antibody-mediated responses. The most common (approximately 95%) or "primary" determinant of penicillin allergy is the penicillin acyl determinant, which is generated by opening the β-lactam ring of penicillin. This allows penicillin to bind to proteins via the amide group. "Secondary" determinants (occurring less frequently) refer to other metabolites, including native penicillin and penicillinic acid. /Penicillin/
Bactericidal agents; inhibit bacterial cell wall synthesis. Its action depends on whether penicillin can 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 weakened bacterial cell walls and eventual lysis. /Penicillin/

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Therapeutic Uses
Penicillin
Naproxil is as potent as oxacillin against penicillinase-producing penicillinase-resistant Staphylococcus aureus, but less active against penicillin-G-sensitive staphylococci. Naproxil is inactivated to varying degrees in the acidic environment of gastric contents.
Although…it is also effective against non-penicillinase-producing streptococci, pneumococci, and gonococci, it is generally not used to treat infections caused by these bacteria unless they are mixed with penicillin-G-resistant staphylococci. /Naproxil Sodium/
Naproxil…inhibits the growth of Escherichia coli and certain other microorganisms that cause urinary tract infections, and…is sometimes used to treat such infections; however, after oral administration, the drug concentration, especially in urine, is usually lower or fluctuates more significantly than with other penicillins, therefore parenteral administration of other penicillins is recommended. For more complete data on the therapeutic uses of nafcillin (14 types), please visit the HSDB record page.

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Drug Warnings
Neutropin was observed in 3 pediatric patients treated with nafcillin at doses of 100–180 mg/kg/day. It is recommended to switch to a non-penicillin antibiotic when the absolute neutrophil count is below 1000/ml.Children receiving intravenous penicillin should undergo white blood cell counts and differential analysis 2–3 times per week. Nafcillin has an unusually high incidence of adverse drug reactions. Because penicillin is excreted in breast milk, breastfeeding women should use nafcillin with caution. Penicillin is excreted in breast milk at low concentrations. Although there are no reports of serious problems in humans, use of penicillin by breastfeeding women may cause allergies, diarrhea, candidiasis, and rashes in infants. /Penicillins/
For more complete data on nafcillin (17 total), please visit the HSDB records page.

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Pharmacodynamics
Nafcillin is a semi-synthetic antibiotic derived from 6-aminopenicillanic acid. This class of drugs is highly resistant to the inactivation of staphylococcal penicillinase and is effective against both penicillinase-producing and non-penicillinase-producing staphylococcal strains.

C21H22N2O5S

414.47478

414.124

147-52-4

Nafcillin sodium monohydrate;7177-50-6;Nafcillin sodium;985-16-0

8982

Typically exists as solid at room temperature

1.4±0.1 g/cm3

714.1±60.0 °C at 760 mmHg

385.7±32.9 °C

0.0±2.4 mmHg at 25°C

1.686

3.52

2

6

5

29

699

3

CCOC1=C(C(N[C@@H]2C(N3[C@H](C(C)(S[C@H]23)C)C(O)=O)=O)=O)C4=CC=CC=C4C=C1

GPXLMGHLHQJAGZ-JTDSTZFVSA-N

InChI=1S/C21H22N2O5S/c1-4-28-13-10-9-11-7-5-6-8-12(11)14(13)17(24)22-15-18(25)23-16(20(26)27)21(2,3)29-19(15)23/h5-10,15-16,19H,4H2,1-3H3,(H,22,24)(H,26,27)/t15-,16+,19-/m1/s1

(2S,5R,6R)-6-[(2-ethoxynaphthalene-1-carbonyl)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.)