Cephalothin

396.44

396.44

205-815-7

R72LW146E6

DTXSID4022783

C62021

Solid

J - Antiinfectives for systemic use

167

-0.4

Solid

1.56 g/cm3

160-160.5 °C

757.2°C at 760 mmHg

411.8ºC

1.675

5.21e-02 g/L

1.7X10-14 mm Hg at 25 deg C (est)

Specific optical rotation = +50 °For D sodium line at 20 °C (c = 1.03 in acetonitrile)

Henry's Law constant = 1.7X10-17 atm-cu m/mol at 25 °C (est)

pKa = 3.8 (carboxylic acid) (est)

Solutions of cephalothin may darken, especially if stored at room temperature. A slight discoloration does not affect potency. Solutions stored under refrigeration may precipitate, but the precipitate can be redissolved by warming to room temperature with constant agitation.

P261, P272, P280, P285, P302+P352, P304+P341, P321, P333+P313, P342+P311, P363, P501

H317

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.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed discontinued drug products, incl cephalothin sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Cephalothin sodium/|The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Cephalothin is included on this list.

Rat intravenous LD50 is 4000 mg/kg.

Concurrent administration with probenecid may prolong the serum half-life of cephalothin.|ANIMAL STUDIES INDICATED THAT FUROSEMIDE ENHANCES NEPHROTOXICITY OF...CEPHALOTHIN...|...CEPHALOSPORINS...MAY BE AFFECTED BY CONCURRENT USE OF SULFINPYRAZONE. DIMINISHED TUBULAR SECRETION OF...WEAK ACIDS COULD RESULT IN HIGHER & MORE SUSTAINED SERUM LEVELS & HENCE, INTENSIFICATION OF DRUG ACTIVITY. /CEPHALOSPORINS/|NON-IONIC, ANIONIC, & ZWITTERIONIC SURFACTANTS INDUCED RAPIDLY REVERSIBLE HYPER-ABSORPTIVE STATE IN THOMAS CANINE FUNDIC POUCH FOR...CEPHALOTHIN...|For more Interactions (Complete) data for CEPHALOTHIN (10 total), please visit the HSDB record page.

LD50 Rat oral >10,000 mg/kg /sodium salt/|LD50 Rat ip 7716 mg/kg /sodium salt/|LD50 Mouse oral >20,000 mg/kg /sodium salt/|LD50 Mouse ip 5670 mg/kg /sodium salt/

Serious bleeding related either to ... thrombocytopenia, and/or platelet dysfunction has been reported with several beta-lactam antibiotics. This appears to be a particular problem with certain patients (elderly, poorly nourished, or those with renal insufficiency) who are receiving moxalactam. /Cephalosporins/

65-80%

Cephalothin's production and use as an antibacterial drug for humans and animals(1-3) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 14(SRC), determined from a log Kow of -0.41(2) and a regression-derived equation(3), indicates that cephalothin is expected to have very high mobility in soil(SRC). An estimated pKa value of 3.8 (carboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(4), indicates that this compound will exist primarily as an anion in the environment and anions generally have higher mobility in soil than their neutral counterparts(5). Volatilization of cephalothin from moist soil surfaces is not expected to be an important fate process(SRC) because anions do not volatilize. Cephalothin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-14 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation data were not available for cephalothin(SRC, 2006).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 14(SRC), determined from a log Kow of -0.41(2) and a regression-derived equation(3), indicates that cephalothin is not expected to adsorb to suspended solids and sediment(SRC). An estimated pKa value of 3.8 (carboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(4), indicates that this compound will exist primarily as an anion in the environment. Volatilization from water surfaces is not expected(SRC) because anions do not volatilize. According to a classification scheme(5), an estimated BCF of 0.3(SRC), from its log Kow(2) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available for cephalothin(SRC, 2006).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cephalothin, which has an estimated vapor pressure of 1.7X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase cephalothin may be removed from the air by wet or dry deposition(SRC). Cephalothin may absorb at wavelengths >290 nm (UV max = 260 nm with a possible shoulder above 290 nm)(3) and therefore may be susceptible to direct photolysis by sunlight(4).

A base-catalyzed second-order hydrolysis rate constant of 3.5X10-1 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 230 and 23 days at pH values of 7 and 8, respectively(1). Cephalothin may absorb at wavelengths >290 nm (UV max = 260 nm with a possible shoulder above 290 nm)(2) and therefore may be susceptible to direct photolysis by sunlight(3).

An estimated BCF of 0.3 was calculated for cephalothin(SRC), using a log Kow of -0.41(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of cephalothin is estimated as 14(SRC), using a log Kow of -0.41(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that cephalothin is expected to have very high mobility in soil. An estimated pKa value of 3.8 (carboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(4), indicates that this compound will exist primarily as an anion in the environment, and anions generally do not adsorb to soils as strongly as their neutral counterparts(5).

An estimated pKa value of 3.8 (carboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(1), indicates that this compound will exist primarily as an anion in the environment. Cephalothin is not expected to volatilize from moist soil or water surfaces(SRC) because anions do not volatilize. Cephalothin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.7X10-14 mm Hg(SRC), determined from a fragment constant method(2).

While data specific to cephalothin were not located(SRC, 2006), the literature suggests that some pharmaceutically active compounds originating from human and veterinary therapy are not eliminated completely in municipal sewage treatment plants and are therefore discharged into receiving waters(1). Wastewater treatment processes often were not designed to remove them from the effluent(2). Selected organic waste compounds may be degrading to new and more persistent compounds that may be released instead of or in addition to the parent compound(2).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 21,013 workers (19,052 of these are female) are potentially exposed to cephalothin in the US(1). Occupational exposure to cephalothin may occur through dermal contact with this compound at workplaces where cephalothin is produced or used(SRC). Exposure to cephalothin among the general population may be limited to those administered this substance as a drug and to those who administer cephalothin to animals(SRC).

Used to prevent infection during surgery and to treat many kinds of infections of the blood, bone or joints, respiratory tract, skin, and urinary tract.

Since, among the cephalosporins, cephalothin is the most impervious to attack by Staphylococcal beta-lactamase, it is very effective in severe Staphylococcal infections, such as endocarditis.|Mesh Heading: anti-bacterial agents|Use should be restricted to treatment of serious infections caused by susceptible organisms, most commonly when patient is hypersensitive to penicillins. /Sodium/|... Cephalosporin is ... drug of first choice ... for Klebsiella infections ... They are useful as alternative choices to penicillin. /Cephalosporins/|For more Therapeutic Uses (Complete) data for CEPHALOTHIN (28 total), please visit the HSDB record page.

Excretion is delayed in presence of decr renal function, and intervals between doses must be lengthened when renal failure is severe.|Cephalothin should not be used to treat bacterial meningitis.|Infections due to Enterococci are usually unaffected by these cmpd ... Enterococcal endocarditis cannot be cured with cephalosporin even when it is given concurrently with gentamicin or streptomycin. /Cephalosporins/|Patients with a history of a mild or a temporally distant reaction to penicillin appear to be at low risk of rash or other allergic reaction following the admin of a cephalosporin ... Patients who have had a recent severe, immediate reaction to a penicillin should be given a cephalosporin with great caution, if at all. /Cephalosporin/|For more Drug Warnings (Complete) data for CEPHALOTHIN (21 total), please visit the HSDB record page.

Resistance to the cephalosporins may be related to inability of the antibiotic to reach its sites of action; to alterations in the penicillin-binding proteins (PBPs) that are targets of the cephalosporins, such that the antibiotics bind with lower affinity; or to bacterial enzymes (beta-lactamases) that can hydrolyze the beta-lactam ring and inactivate the cephalosporin ... The most prevalent mechanism of resistance to cephalosporins is destruction of the cephalosporins by hydrolysis of the beta-lactam ring ...Cefazolin is more susceptible to hydrolysis by beta-lactamase from Staphylococcus aureus than is cephalothin ...|... Some bacteria elaborated an enzyme acting specifically on cephalosporin C to destroy its antibacterial activity. This substance, cephalosporinase, is also a beta-lactamase. /Cephalosporins/

Cefalotin (INN) or cephalothin (USAN) is a semisynthetic first generation cephalosporin having a broad spectrum of antibiotic activity that is administered parenterally.

Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

CEPHALOTHIN ENTERS AQUEOUS HUMOR AFTER SUBCONJUNCTIVAL INJECTIONS YIELDING PEAK LEVELS CA 1-2 HR AFTER DOSING. RATIO OF AQ HUMOR:SERUM ANTIBIOTIC LEVELS RANGES FROM 4.0 TO 67.0 DURING 5 HR AFTER DOSING, & LOSS OF ANTIBIOTIC FROM AQ HUMOR OCCURS BY BIPHASIC PROCESS.|...CEPHALOTHIN...WERE SHOWN...TO PENETRATE INTO BONE TO VERY LIMITED EXTENT AFTER SC OR ORAL DOSES TO RATS. RATIOS OF BONE TO SERUM CONCN AVG 1:4 FOR CEPHALOTHIN... DESPITE DIFFERENCES IN CONCN, T/2 IN BONE & SERUM WERE SIMILAR.|DRUGS RECENTLY SHOWN TO ACTIVELY CROSS HUMAN PLACENTA INCL...CEPHALOTHIN...|Concn of cephalothin present in urine after admin of 1 g range from 0.7 to 5 mg/mL. Excretion is delayed in presence of decr renal function ...|For more Absorption, Distribution and Excretion (Complete) data for CEPHALOTHIN (11 total), please visit the HSDB record page.

Metabolized to a less active desacetyl metabolite, although 50-75% of the drug is eliminated unchanged in the urine.|Approx 25% of cephalothin dose admin was eliminated in urine as deacetylcephalothin.|Cephalothin ... /is/ deacetylated in vivo, and these metabolites have less antimicrobial activity than the parent cmpd ... The deacetylated metabolites also are excreted by the kidneys.

30 minutes|Half-life = 0.6 hr /by/ injection /From table/

The bactericidal activity of cefalotin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). The PBPs are transpeptidases which are vital in peptidoglycan biosynthesis. Therefore, their inhibition prevents this vital cell wall compenent from being properly synthesized.|Bactericidal; action depends on ability to reach and bind penicillin-binding proteins located in bacterial cytoplasmic membranes. Cephalosporins inhibit bacterial septum and cell wall synthesis, probably by action of membrane-bound transpeptidase enzymes. This prevents cross-linkage of peptidoglycan chains, which is necessary for bacterial cell wall strength and rigidity. Also, cell division and growth are inhibited, and elongation of susceptible bacteria and lysis frequently occur. Rapidly dividing bacteria are those most susceptible to the actin of cephalosporins. /Cephalosporins/

Peritoneal dialysis removes all of cephalothin from blood in about 48 hr. Drug is also removed from circulation by hemodialysis ...|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Anaphylaxis presents clinically as the acute onset of peripheral vascular collapse and shock. This may begin minutes after contact with the precipitating allergen. It is the most feared and serious of the allergic reactions and carries with it a significant risk of death. Skin and mucosal lesions, including urticaria and angioedema, may immediately precede the onset of anaphylaxis. Nausea, vomiting, diarrhea, and bronchospasm may occur as part of the acute reaction to the drug. These end-organ responses are initiated by the release of histamine, serotonin, bradykinin and other vasoactive substances released by the basophils and mast cells. ... Penicillins, cephalosporins, and sulfonamides are the antimicrobials most often associated with anaphylactic reactions. /Penicillins and cephalosporins/|/SIGNS AND SYMPTOMS/ Renal insufficiency, manifested by an increase in serum creatinine levels and decrease in creatinine clearance, represents a major adverse effect of the use of polymyxins. Occurrence of hematuria, proteinuria, cylindruria, or oliguria may also be associated with the administration of polymyxins. In addition, acute tubular necrosis can also develop. Histological findings of colistin-induced renal damage usually involve focal irregular dilatation of tubules, epithelial and polymorphonuclear cell cast formation, and degeneration and regeneration of epithelial cells. In addition, separation of tubules by loose collagenous tissue, suggestive of edema, has also been reported. The basement membrane is usually intact, as well as the glomeruli./Polymyxins/|/SIGNS AND SYMPTOMS/ Cephalothin can cause nephrotoxicity, neutropenia, false-positive Coombs' test results, allergic rash, poor passage through blood brain barrier in neonates.|/SIGNS AND SYMPTOMS/ A positive Coombs reaction appears frequently in patients who receive large doses of a cephalosporin. Hemolysis is not usually associated with this phenomenon, although it has been reported. Cephalosporins have produced rare instances of bone-marrow depression, characterized by granulocytopenia ... Serious bleeding related either to ... thrombocytopenia, and/or platelet dysfunction has been reported with several beta-lactam antibiotics. This appears to be a particular problem with certain patients (elderly, poorly nourished, or those with renal insufficiency) who are receiving moxalactam. /Cephalosporins/|For more Human Toxicity Excerpts (Complete) data for CEPHALOTHIN (9 total), please visit the HSDB record page.

Cefalotin

ESSENTIALLY 100% AS AN ANTIBIOTIC (AS SODIUM SALT)

Sterile cephalothin sodium, USP (keflin), is marketed in 10-mL rubber-stoppered vials containing either 1, 2, or 4 g.

Cephalothin is semisynthetic derivative of cephalosporin C ...|CEPHALOSPORINS ARE INCOMPATIBLE WITH ERYTHROMYCIN & TETRACYCLINES IN PARENTERAL MIXTURES. /CEPHALOSPORINS, FROM TABLE/|Cephalosporin C is very resistant to action of penicillinase, for which it is both competitive and noncompetitive inhibitor, depending on substrate tested ... /Cephalosporins/

Analyte: cephalothin; matrix: chemical identification; procedure: ultraviolet absorption spectrophotometry with comparison to standards /cephalothin sodium/|Analyte: cephalothin; matrix: chemical purity; procedure: liquid chromatography with detection at 254 nm and comparison to standards /cephalothin sodium/|Analyte: cephalothin; matrix: pharmaceutical preparation (injection solution); procedure: liquid chromatography with detection at 254 nm and comparison to standards (chemical purity) /cephalothin sodium/|Analyte: cephalothin; matrix: pharmaceutical preparation (solution for injection; may contain sodium bicarbonate); procedure: liquid chromatography with detection at 254 nm and comparison to standards (chemical purity) /cephalothin sodium/|For more Analytic Laboratory Methods (Complete) data for CEPHALOTHIN (9 total), please visit the HSDB record page.

Analyte: cephalothin; matrix: blood (serum); procedure: high-performance liquid chromatography with ultraviolet detection at 254 nm; limit of detection: 3 ug/mL|Analyte: cephalothin; matrix: blood (serum); procedure: high-performance liquid chromatography with ultraviolet detection at 242 nm; limit of detection: 0.3 ng/mL|Analyte: cephalothin; matrix: aqueous humor; procedure: high-performance liquid chromatography with ultraviolet detection at 254 nm|Analyte: cephalothin; matrix: blood (serum); procedure: high-performance liquid chromatography with ultraviolet detection at 240 nm; limit of detection: 500-2000 ng/mL|For more Clinical Laboratory Methods (Complete) data for CEPHALOTHIN (9 total), please visit the HSDB record page.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals