Chemistry - An injectable semi-synthetic cephalosporin antibiotic, cephalothin sodium occurs as apractically odorless, white to off-white, crystalline powder. It is freely soluble in water and veryslightly soluble in alcohol. Each gram of the injection contains 2.8 mEq of sodium. Afterreconstitution the solution for injection has a pH of 6.0-8.5.
Storage, Stability, CompatibilityThe sterile powder for injection and reconstitution should bestored at room temperature. After reconstituting with sterile water for injection, cephalothin sodiumneutral is stable for 12 hours at room temperature and 96 hours when refrigerated. Precipitates mayoccur with refrigerated solutions, but can be redissolved with warming and agitation. Solutions maydarken, particularly at room temperature, but this does not indicate any loss of potency. In thefrozen state, cephalothin sodium solutions are relatively stable.
The following drugs or solutions are reportedly compatible with cephalothin: D25W/Amino
Acids 4.25%, D5W in Lactated Ringer's, D5W in sodium chloride 0.2% - 0.9%, D5W, D10W,
Lactated Ringer's Injection, normal saline, ascorbic acid injection, chloramphenicol sodiumsuccinate, clindamycin phosphate, cytarabine, fluorouracil, heparin sodium, hydrocortisone sodiumsuccinate, magnesium sulfate, metaraminol bitartrate, methotrexate, nitrofurantoin sodium, oxacillinsodium, phytonadione, polymyxin B sulfate, potassium chloride, sodium bicarbonate and vitamin B-complex with C.
The following drugs or solutions are reportedly incompatible or only compatible in specificsituations with cephalothin: amikacin sulfate, aminophylline, bleomycin sulfate, calcium chloride/gluconate, cimetidine HCl, dopamine HCl, doxorubicin HCl, erythromycin lactobionate, gentamicin sulfate, isoproterenol HCl, kanamycin sulfate, norepinephrine bitartrate, oxytetracycline
HCl, penicillin G potassium/sodium, phenobarbital sodium, prochlorperazine edisylate andtetracycline HCl. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used.
It is suggested to consult specialized references for more specific information (e.g., Handbook on
Injectable Drugs by Trissel; see bibliography).
Pharmacology/Spectrum of Activity - A first generation cephalosporin, cephalothin exhibitsactivity against the bacteria usually covered by this class. Refer to the monograph: Cephalosporins,
General Information for more specific information.
Uses, Indications - In the United States, there are no cephalothin products approved for veterinaryspecies, but it has been used clinically in several species when a relatively short-acting, injectable, first generation cephalosporin is indicated.
Pharmacokinetics (specific) - Cephalothin is not appreciably absorbed after oral administrationand must be given parenterally to achieve therapeutic serum levels. Absorbed drug is partiallymetabolized by the liver and kidneys to desacetylcephalothin which is about 25% as active anantibacterial as the parent compound. In humans, about 60-95% of the drug is excreted unchangedinto the urine and 27-54% of a dose is excreted as the desacetyl metabolite. Elimination half-livesmay be significantly prolonged in patients with severely diminished renal function. Pharmacokineticparameters for dogs and horses follow:
In dogs, the apparent volume of distribution at steady state is 435 ml/kg, total body clearance of11.6 - 15 ml/min/kg with a serum elimination half-life of 42-51 minutes.
In horses, the apparent volume of distribution at steady state is 145 ml/kg, total body clearance of13 ml/min/kg with a serum elimination half-life of 15 minutes when given IV and 49 minutes after IM injection. Cephalothin is about 20% bound to equine plasma proteins.