Cefuvex Mechanism of Action

Pharmacology: Pharmacological Action: 1.5 g: Cefuroxime is a second generation cephalosporin. The bactericidal action of cefuroxime results from inhibition of cell-wall synthesis through binding with bacterial protein. Cefuroxime has antibacterial activity against a wide range of pathogenic bacteria, and it is stable in the presence of many kinds of beta-lactamases, especially stable with plasmid mediated-enzyme commonly found in Enterobacteriaceae.
From animal in vitro test and the treatment of clinical infections, it is proven that cefuroxime is usually active against the following bacteria: Aerobes, Gram-positive: Staphylococcus aureus (including beta-lactamase producing bacteria), Streptococcus pneumoniae, and Streptococcus pyogenes.
Aerobes, Gram-negative: Escherichia coli, Haemophilus influenzae (including beta-lactamase producing bacteria), Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella (Branhamella) catarrhalis (including beta-lactamase producing bacteria), Neisseria gonorrhoeae (including beta-lactamase producing bacteria).
Most strains of Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Clostridium difficile, and Bacteroides fragilis have been shown by in vitro tests to be resistant to cefuroxime.
Pharmacokinetics: 750 mg: Cefuroxime sodium (CEFUVEX) is given by intramuscular or intravenous injection. Peak plasma concentrations of about 27 μg per mL have been achieved 45 minutes after an intramuscular dose of 750 mg with measurable amounts presents 8 hours after a dose. Up to 50% of cefuroxime in the circulation is bound to plasma proteins. The plasma half life is about 70 minutes and is prolonged in patients with renal impairment and in neonates.
Cefuroxime is widely distributed in the body including pleural fluid, sputum, bone, synovial fluid and aqueous humor, but only achieves therapeutic concentrations in the CSF when the meninges are inflamed. It crosses the placenta and has been detected in breast milk.
Cefuroxime is excreted unchanged by glomerular filtration and renal tubular secretion, and high concentrations are achieved in the urine. Following injection, most of a dose of cefuroxime is secreted within 24 hours, the majority within 6 hours. Probenecid competes for renal tubular secretions with cefuroxime resulting in higher and more prolonged plasma concentrations of cefuroxime. Small amounts of cefuroxime are excreted in bile.
Plasma concentrations are reduced by dialysis.
1.5 g: After I.M. injection of a 750-mg dose of cefuroxime to normal volunteers, the mean peak serum concentration was 27 μg/mL. The peak occurred at approximately 45 minutes (range, 15 to 60 minutes). Following I.V. doses of 750 mg and 1.5 g, serum concentrations were approximately 50 and 100 μg/mL, respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2 μg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively. There was no evidence of accumulation of cefuroxime in the serum following I.V. administration of 1.5-g doses every 8 hours to normal volunteers. The serum half-life after either I.M. or I.V. injections is approximately 80 minutes.
Approximately 89% of a dose of cefuroxime is excreted by the kidneys over an 8-hour period, resulting in high urinary concentrations.
Following the I.M. injection of a 750-mg single dose, urinary concentrations averaged 1300 μg/mL during the first 8 hours. I.V. injection doses of 750 mg and 1.5 g produced urinary levels averaging 1150 and 2500 μg/mL, respectively, during the first 8-hour period.
The concomitant oral administration of probenecid with cefuroxime slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Cefuroxime is detectable in therapeutic concentrations in pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor.
Cefuroxime is detectable in therapeutic concentrations in cerebrospinal fluid (CSF) of adults and pediatric patients with meningitis. Cefuroxime concentration can be detected in cerebrospinal fluid during multiple dosing of patients with meningitis.
Cefuroxime is approximately 50% bound to serum protein.
Toxicology: Genotoxicity: 1.5 g: Although potential carcinogenicity of this drug is not evaluated by animal lifelong study, mutagenic action of this drug is not found in micronucleus test and bacterial test.
Reproductive toxicity: 1.5 g: Cefuroxime does not damage the reproductive capacity of rats with a dose of 1000 mg/Kg/day, and there is no damage to the growth of fetus of rats and mice with a dose of 3200 mg/Kg/day. But the pertinence between animal and human is still not established by clinical study.