Following IM administration of a single 500 mg or 1 g dose of CLAFORAN to normal volunteers, mean peak serum concentrations of 11.7 and 20.5 µg/mL respectively were attained within 30 minutes and declined with an elimination half-life of approximately 1 hour. There was a dose-dependent increase in serum levels after the IV administration of 500 mg, 1 g, and 2 g of CLAFORAN (38.9, 101.7, and 214.4 µg/mL respectively) without alteration in the elimination half-life. There is no evidence of accumulation following repetitive IV infusion of 1 g doses every 6 hours for 14 days as there are no alterations of serum or renal clearance. About 60% of the administered dose was recovered from urine during the first 6 hours following the start of the infusion.

Approximately 20-36% of an intravenously administered dose of ¹⁴C-cefotaxime is excreted by the kidney as unchanged cefotaxime and 15-25% as the desacetyl derivative, the major metabolite. The desacetyl metabolite has been shown to contribute to the bactericidal activity. Two other urinary metabolites (M₂ and M₃) account for about 20-25%. They lack bactericidal activity.

A single 50 mg/kg dose of CLAFORAN was administered as an intravenous infusion over a 10- to 15- minute period to 29 newborn infants grouped according to birth weight and age. The mean half-life of cefotaxime in infants with lower birth weights (<1500 grams), regardless of age, was longer (4.6 hours) than the mean half-life (3.4 hours) in infants whose birth weight was greater than 1500 grams. Mean serum clearance was also smaller in the lower birth weight infants. Although the differences in mean half-life values are statistically significant for weight, they are not clinically important. Therefore, dosage should be based solely on age. (See DOSAGE AND ADMINISTRATION section.)

Additionally, no disulfiram-like reactions were reported in a study conducted in 22 healthy volunteers administered CLAFORAN and ethanol.

Microbiology

The bactericidal activity of cefotaxime sodium results from inhibition of cell wall synthesis. Cefotaxime sodium has in vitro activity against a wide range of gram-positive and gram-negative organisms. CLAFORAN has a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria. Cefotaxime sodium has been shown to be a potent inhibitor of ß-lactamases produced by certain gram-negative bacteria. Cefotaxime sodium is usually active against the following microorganisms both in vitro and in clinical infections (see INDICATIONS AND USAGE).

Aerobes, Gram-positive:

• Enterococcus spp.
• Staphylococcus aureus* , including (beta)-lactamase-positive and negative strains
• Staphylococcus epidermidis
• Streptococcus pneumoniae
• Streptococcus pyogenes (Group A beta-hemolytic streptococci)
• Streptococcus spp.

Aerobes, Gram-negative:

• Citrobacter species,
• Enterobacter species,
• Escherichia coli,
• Haemophilus influenzae (including ampicillin-resistant H. Influenzae),
• Haemophilus parainfluenzae,
• Klebsiella species (including K. pneumoniae),
• Neisseria gonorrhoeae (including penicillinase and non-penicillinase producing strains),
• Neisseria meningitidis,
• Proteus mirabilis,
• Proteus vulgaris,
• Proteus inconstans Group B,
• Morganella morganii,
• Providencia rettgeri,
• Serratia species, and
• Acinetobacter species.

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