Veterinary Drug Handbook (VDH) is the reference veterinarians turn to when they want an independent source of information on the drugs that are used in veterinary medicine today.

CEFOTAXIME SODIUM

For general information on the cephalosporins including adverse effects, contraindications, overdosage, drug interactions, and monitoring parameters, refer to the monograph: Cephalosporins, General Information.
Chemistry - A semisynthetic, 3rd generation, aminothiazolyl cephalosporin, cefotaxime sodium occurs as an odorless, white to off-white crystalline powder with a pKa of 3.4. It is sparingly soluble in water and slightly soluble in alcohol. Potency of cefotaxime sodium is expressed in terms of cefotaxime. One gram of cefotaxime (sodium) contains 2.2 mEq of sodium.

Storage, Stability, Compatibility

Cefotaxime sodium sterile powder for injection should bestored at temperatures of less than 30°C; protect from light. The commercially available frozeninjection should be stored at temperatures no greater than -20°C. Depending on storage conditions, the powder or solutions may darken which may indicate a loss in potency.
All commonly used IV fluids and the following drugs are reportedly compatible with cefotaxime:metronidazole and verapamil. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for more specificinformation (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology/Spectrum of Activity - Cefotaxime has a relatively wide spectrum of activityagainst both gram positive and gram negative bacteria. While less active against Staphylococcusspp. than the first generation agents, it still has significant activity against those and other grampositive cocci. Cefotaxime, like the other 3rd generation agents, has extended coverage of gramnegative aerobes particularly in the family Enterobacteriaceae, including Klebsiella sp., E. coli,
Salmonella, Serratia marcesans, Proteus sp., and Enterobacter sp.. Cefotaxime's in vitro activityagainst Pseudomonas aeruginosa is variable and results are usually disappointing when the drug isused clinically against this organism. Many anaerobes are also susceptible to cefotaxime, includingstrains of Bacteroides fragilis, Clostridium sp., Fusobacterium sp., Peptococcus sp., and Peptostreptococcus sp..
Because 3rd generation cephalosporins exhibit specific activities against bacteria, a 30 microgramscefotaxime disk should be used when performing Kirby-Bauer disk susceptibility tests for thisantibiotic.
Uses, Indications - In the United States, there are no cefotaxime products approved for veterinaryspecies, but it has been used clinically in several species when an injectable 3rd generationcephalosporin may be indicated.
Pharmacokinetics (specific) - Cefotaxime is not appreciably absorbed after oral administrationand must be given parenterally to attain therapeutic serum levels. After administration, the drug iswidely distributed in body tissues, including bone, prostatic fluid (human), aqueous humor, bile, ascitic and pleural fluids. Cefotaxime crosses the placenta and activity in amniotic fluid either equalsor exceeds that in maternal serum. Cefotaxime also is distributed into milk in low concentrations. Inhumans, approximately 13-40% of the drug is bound to plasma proteins.
Unlike the first generation cephalosporins (and most 2nd generation agents), cefotaxime will enterthe CSF in therapeutic levels (at high dosages) when the patient's meninges are inflamed.
Cefotaxime is partially metabolized by the liver to desacetylcefotaxime which exhibits someantibacterial activity. Desacetylcefotaxime is partially degraded to inactive metabolites by the liver.
Cefotaxime and its metabolites are primarily excreted in the urine. Because tubular secretion isinvolved in the renal excretion of the drug, probenecid has been demonstrated in several species toprolong the serum half-life of cefotaxime.
Pharmacokinetic parameters in certain veterinary species follow: In dogs, the apparent volume of distribution at steady state is 480 ml/kg, and a total body clearance of 10.5 ml/min/kg after intravenous injection. Serum elimination half-lives of 45 minutes when given IV, 50 minutes after IM injection, and 103 minutes after SQ injection have been noted. Bioavailability is about 87% after IM injection and approximately 100% after SQ injection.
In cats, total body clearance is approximately 3 ml/min/kg after intravenous injection and the serum elimination half-life is about 1 hour. Bioavailability is about 93-98% after IM injection.
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