Chemical formula: C₁₅H₁₇N₅O₆S₂ Molecular mass: 427.455 g/mol PubChem compound: 6335986
Like other beta-lactam drugs, cefpodoxime exerts antibacterial activity by binding to and inhibiting the action of certain bacterial cell wall synthetic enzymes, namely the penicillin binding proteins. This results in the interruption of cell wall (peptidoglycan) biosynthesis, which leads to bacterial cell lysis and death.
Bacterial resistance to cefpodoxime may be due to one or more of the following mechanisms:
Cefpodoxime proxetil is taken up in the intestine and is hydrolysed to the active metabolite cefpodoxime. When cefpodoxime proxetil is administered orally to fasting subjects as a tablet corresponding to 100 mg of cefpodoxime, 51.1% is absorbed and absorption is increased by food intake.
The volume of distribution is 32.3 l and peak levels of cefpodoxime occur 2 to 3 hours after dosing. The maximum plasma concentration is 1.2 mg/L and 2.5 mg/L after doses of 100 mg and 200 mg respectively. Following administration of 100 mg and 200 mg twice daily over 14.5 days, the plasma pharmacokinetic parameters of cefpodoxime remain unchanged.
Serum protein binding of cefpodoxime, 40% principally to albumin. This binding is non-saturable in type.
Concentrations of cefpodoxime in excess of the minimum inhibitory levels (MIC) for common pathogens can be achieved in lung parenchyma, bronchial mucosa, pleural fluid, tonsils, interstitial fluid and prostate tissue.
As the majority of cefpodoxime is eliminated in the urine, the concentration is high. (Concentrations in 0-4, 4-8, 8-12 hour fractions after a single dose exceed MIC 90 of common urinary pathogens). Good diffusion of cefpodoxime is also seen into renal tissue, with concentrations above MIC 90 of the common urinary pathogens, 3-12 hours after an administration of a single 200 mg dose (1.6–3.1 μG/G). Concentrations of cefpodoxime in the medullary and cortical tissues is similar.
Studies in healthy volunteers show medium concentrations of cefpodoxime in the total ejaculate 6-12 hours following administration of a single 200 mg dose to be above the MIC 90 of N. gonorrhoeae.
Cefpodoxime proxetil is a prodrug of cefpodoxime. Essentially the entire drug that is absorbed is de-esterified, pre-systemically in the small intestine to its active form. Cefpodoxime itself does not undergo any significant metabolism and is excreted unchanged, largely in the urine.
The main route of excretion is renal, 80% is excreted unchanged in the urine with an elimination half-life of approximately 2.4 hours.
In children, studies have shown the maximum plasma concentration occurs approximately 2-4 hours after dosing. A single 5 mg/kg dose in 4-12 year olds produced a maximum concentration similar to that in adults given a 200 mg dose.
In patients below 2 years receiving repeated doses of 5 mg/kg 12 hourly, the average plasma concentrations, 2 hours post dose, are between 2.7 mg/L (1-6 months) and 2.0 mg/L (7 months-2 years).
In patients between 1 month and 12 years receiving repeated doses of 5 mg/kg 12 hourly, the residual plasma concentrations at steady state are between 0.2-0.3 mg/L (1 month-2 years) and 0.1 mg/L (2-12 years).
Non-clinical data reveal no special hazard for humans based on conventional studies of single dose toxicity, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.
Long-term animal carcinogenesis studies of cefpodoxime proxetil have not been performed. Mutagenesis studies of cefpodoxime, including the Ames test both with and without metabolic activation, the chromosome aberration test, the unscheduled DNA synthesis assay, mitotic recombination and gene conversion, the forward gene mutation assay and the in vivo micronucleus test, were all negative. No untoward effects on fertility or reproduction were noted when 100 mg/kg/day or less (2 times the human dose based on mg/m²) was administered orally to rats.
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