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 administration of 500mg nafcillin, the mean plasma concentration was approximately 30 µg/mL. This value was reached after 5 minutes of injection.
Nafcillin is primarily eliminated by non-renal routes, namely hepatic inactivation and excretion in the bile.
Nafcillin is reported to be widely distributed in various body fluids, including bile, pleural, amniotic and synovial fluids.
...ABSORPTION AFTER ORAL ADMIN IS IRREGULAR...WHETHER...TAKEN WITH MEALS OR ON EMPTY STOMACH. AFTER PARENTERAL ADMIN, PLASMA CONCN OF NAFCILLIN IS LOWER THAN...EQUIV DOSE OXACILLIN. THIS IS ASSOC WITH...LARGER APPARENT VOL DISTRIBUTION OF NAFCILLIN, RESULTING FROM SELECTIVE SEQUESTRATION...IN LIVER & POSSIBLY OTHER TISSUE
...BOUND TO PLASMA PROTEIN TO EXTENT OF ABOUT 90%. ONLY APPROX 10% OF ORAL DOSE...RECOVERABLE IN URINE. PROBENECID FURTHER REDUCES EXCRETION IN URINE. MAJOR CHANNEL OF ELIMINATION...IS BILE...ABOUT 90% OF SINGLE IV DOSE... ACCOUNTED FOR BY BILIARY EXCRETION; THERE IS SOME REABSORPTION OF DRUG FROM SMALL INTESTINE.
PEAK CONCN OF NAFCILLIN IN BILE ARE WELL ABOVE THOSE FOUND IN PLASMA.
A 1 G ORAL DOSE NAFCILLIN SODIUM REACHED BLOOD CONCN 0.7 MG% @ 1 HR; 0.5 G IM DOSE REACHED CONCN 0.6 MG% @ 1 HR. 17% OF AN ORAL DOSE WAS EXCRETED IN URINE; 36% OF IM DOSE WAS EXCRETED IN URINE. /NAFCILLIN SODIUM/
For more Absorption, Distribution and Excretion (Complete) data for NAFCILLIN (19 total), please visit the HSDB record page.

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Metabolism / Metabolites
Hepatic metabolism accounts for less than 30% of the biotransformation of most penicillins.
...PROTON-CATALYZED HYDROLYSIS /OF PENICILLINS/ TO YIELD PENICILLOIC ACIDS IS WELL DOCUMENTED...CATALYZED BY BACTERIAL BETA-LACTAMASE & BY MAMMALIAN ENZYMES. /PENICILLINS/
NAFCILLIN GIVES 2-ETHOXY-1-NAPHTHAMIDOPENICILLOIC ACID IN BACILLUS. /FROM TABLE/
Approx 60% of a dose of nafcillin is metabolized in the liver to inactive metabolites.

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Biological Half-Life
The serum half-life of nafcillin administered by the intravenous route ranged from 33 to 61 minutes as measured in three separate studies.
NORMAL T1/2 OF NAFCILLIN IS 0.5 HR. /FROM TABLE/
The serum half-life of nafcillin in adults with normal renal and hepatic function averages 0.5-1.5 hr. In one study in healthy adults, nafcillin had a distribution half-life ... of 0.17 hr and an elimination half-life ... of 1.02 hr.
The serum half-life of ... /nafcillin/ is reportedly 1.2-1.9 hr in patients with creatinine clearances of 3-59 ml/min per 1.73 sq meters and 1.8-2.8 hr in patients with creatinine clearances less than 3 ml/min per 1.73 sq meters.
In one study in patients with cirrhosis or extrahepatic biliary obstruction, the t1/2alpha of nafcillin averaged 0.26 or 0.29 hr, respectively, and the t1/2beta averaged 1.2 and 1.7 hr, respectively. Serum clearance of the drug in these patients was lower than in patients with normal renal and hepatic function and averaged 291.5 ml/min in those with cirrhosis and 163.4 ml/min in those with extrahepatic obstruction.
In children 1 mo to 14 yr of age, the serum half-life of nafcillin ranges from 0.75-1.9 hr. Serum concn of nafcillin are generally higher and the serum half-life is longer in neonates than in older children. In one study, the serum half-life of nafcillin ranged from 2.2-5.5 hr in neonates 3 wk of age or younger and 1.2-2.3 hr in neonates 4-9 wk of age.

Hepatotoxicity
The serum aminotransferase elevations that appear during high dose intravenous therapy with oxacillin do not appear to occur with high doses of nafcillin, and patients who develop elevated serum aminotransferase levels while on high dose oxacillin can be safety switched to intravenous nafcillin or other penicillin antibiotics. Only rare instances of clinically apparent hepatotoxicity have been linked to use of nafcillin. Typically, the injury has been a cholestatic hepatitis that arises 1 to 6 weeks after starting nafcillin and can be prolonged, but ultimately resolves. Rash, fever and eosinophilia are uncommon but can occur (Case 1). The injury is similar to that described with flucloxacillin and cloxacillin but is far less frequent with nafcillin. Autoantibodies are uncommon.
Likelihood score: C (probable rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Although no information is available on the use of nafcillin during breastfeeding, penicillins are generally 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. Nafcillin 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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Protein Binding
The degree of nafcillin binding to serum proteins is 89.9 ± 1.5%, where it is mainly bound to albumin.

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Interactions
SERUM BINDING OF...NAFCILLIN...IS REDUCED WHEN ADMIN CONCURRENTLY WITH ASPIRIN.
CHLORAMPHENICOL MAY ANTAGONIZE ACTION OF PENICILLINS. /PENICILLINS/
...ALL...PENICILLINS & ERYTHROMYCINS MAY THEORETICALLY BE EXPECTED TO.../EXHIBIT SYNERGISTIC ANTIBACTERIAL ACTIVITY/. /PENICILLINS/
TETRACYCLINE MAY ANTAGONIZE BACTERICIDAL EFFECT OF PENICILLIN /G/...ANTAGONISM OF ACTION OF ALL...PENICILLINS MIGHT BE EXPECTED. /PENICILLINS/
For more Interactions (Complete) data for NAFCILLIN (14 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 in which the substituent at position 6 of the penam ring is a (2-ethoxy-1-naphthoyl)amino group. It has a role as an antibacterial drug. It is a penicillin and a penicillin allergen. It is a conjugate acid of a nafcillin(1-).
A semi-synthetic antibiotic related to penicillin, Naficillin is a narrow-spectrum beta-lactam antibiotic drug. It is a beta-lactamase-resistant penicillin that is indicated for the treatment of Staphylococcal infections caused by strains that are resistant to other penicillins, except those caused by MRSA. It may be used as a first-line therapy in Methicillin-Sensitive *Staphylococcus aureus* infections.
Nafcillin is a Penicillin-class Antibacterial.
Nafcillin is a parenteral, second generation penicillinase-resistant penicillin antibiotic used largely to treat moderate to severe staphylococcal infections. Nafcillin has been linked to rare occurrences of clinically apparent, idiosyncratic liver injury.
Nafcillin is a semi-synthetic naphthalene and beta-lactam antibiotic with antibacterial activity. Nafcillin inhibits bacterial wall synthesis by a mechanism of action similar to penicillin. Penicillinase-resistant Nafcillin is used to treat infections caused by penicillin-resistant strains of Staphylococci. (NCI04)
A semi-synthetic antibiotic related to penicillin.
See also: Nafcillin Sodium (has salt form).

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Drug Indication
Indicated in the treatment of infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drug.
FDA Label

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Mechanism of Action
Like other penicillins, nafcillin exerts a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication in the bacterial cell wall synthesis. It inhibits the biosynthesis of the bacterial cell wall by forming covalent bonds with penicillin-binding proteins that play a critical role in the final transpeptidation process. Binding to penicillin-binding proteins inhibits the transpeptidase and carboxypeptidase activities conferred by these proteins and prevents the formation of the crosslinks.
SODIUM NAFCILLIN & METHICILLIN ARE GOOD EXAMPLES OF A STRUCTURAL DESIGN THAT INHIBITS BETA-LACTAM HYDROLYSIS BY STERIC CROWDING. /SODIUM NAFCILLIN/
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
NAFCILLIN IS SIMILAR TO OXACILLIN IN ITS POTENCY AGAINST /PENICILLINASE-PRODUCING/ PENICILLIN G-RESISTANT STAPH AUREUS, BUT NOT AS ACTIVE AS PENICILLIN G AGAINST STAPHYLOCOCCI SENSITIVE TO THE LATTER AGENT. NAFCILLIN IS INACTIVATED TO A VARIABLE DEGREE IN ACIDIC MEDIUM OF GASTRIC CONTENTS.
ALTHOUGH...ALSO EFFECTIVE AGAINST NON-PENICILLINASE-PRODUCING STREPTOCOCCI, PNEUMOCOCCI, & GONOCOCCI, IT IS USUALLY NOT USED TO TREAT INFECTIONS CAUSED BY THESE BACTERIA UNLESS THEY ARE PART OF A MIXED INFECTION WITH PENICILLIN G-RESISTANT STAPHYLOCOCCI. /NAFCILLIN SODIUM/
NAFCILLIN...SUPPRESSES GROWTH OF E COLI & CERTAIN OTHER ORGANISMS THAT CAUSE URINARY TRACT INFECTIONS, &...IS SOMETIMES USED TO TREAT SUCH INFECTIONS; HOWEVER, AFTER ORAL ADMIN, ESP, URINE LEVELS OF DRUG ARE GENERALLY LOWER THAN WITH...OTHER PENICILLINS OR TOO ERRATIC, SO PARENTERAL ADMIN OF OTHER PENICILLINS...PREFERRED.
For more Therapeutic Uses (Complete) data for NAFCILLIN (14 total), please visit the HSDB record page.

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Drug Warnings
3 PEDIATRIC PATIENTS ON 100-180 MG/KG/DAY NAFCILLIN DEVELOPED NEUTROPENIA. RECOMMENDED THAT ABSOLUTE NEUTROPHIL COUNT LESS THAN 1000/ML INDICATES CHANGE TO NON-PENICILLIN ANTIBIOTIC. CHILDREN ON IV PENICILLINS SHOULD HAVE WBC COUNTS WITH DIFFERENTIAL ANALYSIS 2-3 TIMES/WK.
UNUSUALLY HIGH OCCURRENCE OF DRUG REACTIONS WITH NAFCILLIN.
Because penicillins are distributed into milk, nafcillin should be used with caution in nursing women.
Penicillins are distributed into breast milk, some in low concentrations. Although significant problems in humans have not been documented, the use of penicillins by nursing mothers may lead to sensitization, diarrhea, candidiasis, and skin rash in the infant. /Penicillins/
For more Drug Warnings (Complete) data for NAFCILLIN (17 total), please visit the HSDB record page.

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Pharmacodynamics
Nafcillin is a semisynthetic antibiotic substance derived from 6-amino-penicillanic acid. The drugs in this class are highly resistant to inactivation by staphylococcal penicillinase and are active against penicillinase-producing and non penicillinase-producing strains of Staphylococcus species.

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.)