147-52-4CCOc1ccc2ccccc2c1C(=O)N[C@@H]1C(=O)N2[C@@H]1SC(C)(C)[C@@H]2C(=O)OGPXLMGHLHQJAGZ-JTDSTZFVSA-NNafcillin 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-).
Pharmaceuticals -> Listed in ZINC15
Pharmaceuticals -> Antibiotics
Soluble
NOT MORE THAN SLIGHT CHARACTERISTIC ODOR; WHITE TO YELLOWISH WHITE POWDER; FREELY SOL IN WATER & CHLOROFORM, SOL IN ALCOHOL /NAFCILLIN SODIUM/
1.72e-02 g/L
Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antibacterial Agents; Penicillins
Pharmaceuticals
Access group antibiotics
STABLE @ ROOM TEMP FOR 2-4 YR /DRY STATE/ DEPENDING ON DOSAGE FORM
ORAL SOLN AFTER RECONSTITUTION WITH DILUENT SHOULD BE STORED @ 2-8 °C /DISCARD UNUSED SOLN AFTER 1 WK/
STABLE FOR 24 HR IN 1/6 MOLAR SODIUM LACTATE INJECTION WHEN STORED @ ROOM TEMP IN CONCN OF 30 MG/ML
LESS THAN 10% ACTIVITY LOST @ ROOM TEMP IN 24 HR (0.905% SODIUM CHLORIDE, 5% DEXTROSE IN 0.45% SODIUM CHLORIDE OR RINGER SOLN)
For more Stability/Shelf Life (Complete) data for NAFCILLIN (10 total), please visit the HSDB record page.
Danger
H317 (100%): May cause an allergic skin reaction [Warning Sensitization, Skin]
P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 3 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
Commercially available nafcillin sodium capsules and tablets should be stored in tight containers at a temperature less than 40 °C, preferably between 15-30 °C; the tablets should also be protected from light. /Nafcillin sodium/
Nafcillin sodium powder for injection should be stored @ room temperature or colder. /Nafcillin sodium/
SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.
J - Antiinfectives for systemic use
QJ - Antiinfectives for systemic use
J01CF02
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.
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/
현재 필터 조건에 해당하는 반응 기록이 없습니다.
불러오는 중…
147-52-4、985-16-0DTXSID8023343CHEMBL1443CHEBI:7447202 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with Waters Major Mix]
197.59 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]
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.
Only rare instances of clinically apparent hepatotoxicity have been linked touse of nafcillin. Typically, the injury is a cholestatic hepatitis thatarises 1 to 6 weeks after starting nafcillin and can be prolonged butultimately resolves. Rash, fever, and eosinophilia are uncommon but canoccur (Case 1). The injury is much like that described with flucloxacillinand cloxacillin but is less frequent with nafcillin. Autoantibodies areuncommon. These favorable outcomes are typical but not invariable. At leastone instance of acute liver failure and one with persistent cholestasis andvanishing bile duct syndrome have been reported. Interestingly, thepersistent serum aminotransferase elevations that are common during highdose intravenous therapy with oxacillin appear to be rare with high doses ofintravenous nafcillin. In several reports of patients who developed elevatedserum aminotransferase levels while on high dose oxacillin, switching tointravenous nafcillin or other penicillin antibiotics was done withoutrecurrence of the liver injury. This may relate to the peak doses chosen forintravenous oxacillin versus nafcillin.
Renal, hepatic, and hematologic systems should be evaluated periodically during prolonged therapy with nafcillin. Because adverse hematologic effects have occurred during therapy with penicillinase-resistant penicillins, total and differential leukocyte counts should be performed prior to initiation of therapy and 1-3 times weekly during therapy. In addition, urinalysis should be performed and BUN and serum creatinine, AST (SCOT), and ALT (SGPT) concn should be determined prior to and periodically during therapy.
SEE PENICILLINS. MASSIVE IV DOSES...(20-60 MILLION UNITS/DAY...) MAY RESULT IN ENCEPHALOPATHY WITH MUSCULAR HYPERIRRITABILITY, MYOCLONUS, VISUAL & AUDITORY HALLUCINATIONS & GENERALIZED CONVULSIONS. /PENICILLINS/
OF 29 STAPH AUREUS PATIENTS TREATED WITH 12 G/DAY IV NAFCILLIN, 4 HAD FEVER, RASH, & LEUKOPENIA; 1 HAD ABSOLUTE NEUTROPENIA.
EFFECT IS MOST LIKELY DUE TO DIRECT TOXIC EFFECT ON BONE MARROW. USUALLY OCCURS DURING 3RD WK THERAPY & REMITS WITH DRUG CESSATION.
HYPOKALEMIA WAS ASSOCIATED WITH NAFCILLIN ADMINISTRATION.
For more Human Toxicity Excerpts (Complete) data for NAFCILLIN (46 total), please visit the HSDB record page.
Drug-Induced Liver Injury Severity and Toxicity (DILIst)
nafcillin
DILI Positive
Intravenous
DOI:10.1016/j.drudis.2019.09.022
IN MICE, RATS, RABBITS...DEATH FROM RESP FAILURE WITH OR WITHOUT CONVULSIONS OCCURRED 6-18 HR AFTER SINGLE ORAL DOSES. ACUTE GASTROENTERITIS & CARDIOVASCULAR SHOCK WERE ASSOC PHENOMENA. /PENICILLINS/
/IN GUINEA PIGS,/ DEATH FROM RESP FAILURE WITH OR WITHOUT CONVULSIONS OCCURRED 6-18 HR AFTER SINGLE ORAL DOSES. ACUTE GASTROENTERITIS & CARDIOVASCULAR SHOCK... ALSO...A LATE (1-2 WK) & GRADUALLY DEVELOPING TOXEMIA KILLED ALL SURVIVORS OF ACUTE RESPONSE. /PENICILLINS/
IN HAMSTERS THE DRUG IS SOMEWHAT MORE TOXIC BY THE ORAL THAN BY THE SC ROUTE WHEN OBSERVED FOR 14 DAYS AFTER SINGLE DOSES. TOLERANCE DEVELOPED TO MULTIPLE DOSING. PERHAPS THE SENSITIVITY OF GUINEA PIGS IS RELATED TO EFFECTS ON INTESTINAL MICROFLORA. /PENICILLINS/
...CATS & DOGS...DEATH FROM RESP FAILURE WITH OR WITHOUT CONVULSIONS OCCURRED 6-18 HR AFTER SINGLE ORAL DOSES. ACUTE GASTROENTERITIS & CARDIOVASCULAR SHOCK WERE ASSOC PHENOMENA. /PENICILLINS/
For more Non-Human Toxicity Excerpts (Complete) data for NAFCILLIN (6 total), please visit the HSDB record page.
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
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.
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.
4CNZ27M7RV
NAFCILLIN
Established Pharmacologic Class [EPC] - Penicillin-class Antibacterial
Chemical Structure [CS] - Penicillins
Nafcillin is a Penicillin-class Antibacterial.
NAFCILLIN
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.
MEDICATION
MEDICATION (VET)
6-AMINOPENICILLANIC ACID IS ACYLATED BY TREATMENT WITH 2-ETHOXY-1-NAPHTHOYL CHLORIDE IN ANHYDROUS ORG SOLVENT CONTAINING TRIETHYLAMINE. AQ EXTRACT OF THIS...IS ADMIXED WITH WATER-IMMISCIBLE SOLVENT & NAFCILLIN PPTD BY ADDN OF SULFURIC ACID. NAFCILLIN SODIUM IS PPTD BY MIXING ETHANOLIC SOLN OF ACID & SODIUM ETHYLHEXANOATE
POWDER FOR INJECTION IS BUFFERED WITH 40 MG SODIUM CITRATE/G OF DRUG; CAPSULES & TABLETS ARE BUFFERED WITH CALCIUM CARBONATE.
NAFCILLIN SODIUM, USP (UNIPEN)...AVAILABLE FOR ORAL & PARENTERAL USE. CAPSULES USUALLY CONTAIN 250 MG...DRUG. SOLN IS ALSO MARKETED FOR ORAL USE. STERILE PREPN FOR INJECTION...AMPULS CONTAINING 500 MG, 1 G, OR 2 G OF SALT. /NAFCILLIN SODIUM/
...A SEMISYNTHETIC PENICILLIN, DERIVED FROM 6-AMINOPENICILLANIC ACID, IS HIGHLY RESISTANT TO PENICILLINASE...
PATENTS: US PATENT 3,157,639. /NAFCILLIN SODIUM/
POTENCY: NOT LESS THAN 820 UG OF NAFCILLIN/MG. /NAFCILLIN SODIUM/
Doyle et al. Brit pat 880,400 (1961 to Beecham) /Nafcillin sodium/
용도Antibacterial.