Pharmacotherapeutic group: Third generation cephalosporins
ATC code: J01DD13
Cefpodoxime proxetil is a beta-lactam antibiotic, a third generation oral cephalosporin. It is the prodrug of cefpodoxime.
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:
Breakpoints: The following limits (MIC breakpoints) are proposed to distinguish sensitive from resistant organisms: Sensitive ≤1 mg/l, resistant >4 mg/l.
The prevalence of acquired resistance may vary geographically and with species over time, therefore, particularly when treating severe infections, local information on resistance is desirable. The use of cefpodoxime proxetil should be based on the local prevalence of resistance and expert advice should be sought when appears questionable for at least some types of infections. Especially in serious infections or treatment failure with a microbiological diagnosis with detection of the pathogen and its susceptibility to cefpodoxime proxetil is desirable. The following table shows the sensitivity of each category of relevant species compared with cefpodoxime proxetil.
Prevalence of acquired resistance in Germany, based on data from the last 5 years of national resistance monitoring projects and studies (December 2010):
Aerobes, Gram-positive microorganisms:
Staphylococcus aureus (methicillin sensitive)
Streptococcus pneumoniae
Streptococcus pyogenes
Aerobes, Gram negative microorganisms:
Haemophilus influenzae
Neisseria gonorrhoeae°°
Proteus mirabilis%
Aerobic, Gram-positive microorganisms:
Staphylococcus aureus$#
Staphylococcus epidermidis$+
Staphylococcus haemolyticus$+
Staphylococcus hominis$+
Staphylococcus saprophyticus$°
Streptococcus pneumoniae (Penicillin-intermediate)
Aerobic, Gram-negative microorganisms:
Citrobacter freundii$
Enterobacter cloacae$
Escherichia coli%&
Klebsiella pneumoniae%
Serratia marcescens°$
Moraxella catarrhalis
Aerobic, Gram-positive microorganisms:
Enterococcus spp.
Staphylococcus aureus (Methicillin resistant)
Streptococcus pneumoniae (Penicillin resistant)
Aerobic, Gram-negative microorganisms:
Morganella morganii
Pseudomonas aeruginosa
Chlamydia spp.
Chlamydophila spp.
Legionella pneumophila
Mycoplasma spp.
° When publishing the table, no data were available in the primary literature, standard works and treatment recommendations sensitivity is assumed
$ The natural susceptibility of most isolates is in the intermediate area
+ In at least one region, the resistance rate is over 50%
% Extended Spectrum Beta-Lactamase (ESBL) producing strains are always resistant
& When isolates from patients with uncomplicated cystitis, the resistance rate <10%, ≥10%
# In the outpatient area resistance rate is <10%
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.
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