Simplicef: Product Information (Page 2 of 3)

CLINICAL PHARMACOLOGY

Pharmacokinetics/Pharmacodynamics

Cefpodoxime proxetil is a prodrug that is absorbed from and de-esterified in the gastrointestinal tract to its active metabolite, cefpodoxime. Following oral administration to fasting Beagles, oral bioavailability was 63.1 ± 5.3%.

Figure 1. Canine Plasma Concentration of Cefpodoxime After a Single Oral Dose of 10 mg/kg Cefpodoxime Proxetil Tablets

Graph
(click image for full-size original)

Cefpodoxime is distributed in the body with an apparent volume of distribution of 151 ± 27 mL/kg. Like other β-lactam antibiotics, cefpodoxime is eliminated from the body primarily in the urine, with an apparent elimination half-life of approximately 5-6 hours after oral administration. This is similar to the 4.7 hour apparent elimination half-life observed after intravenous dosing. Following intravenous administration of 10 mg/kg, the average total body clearance (ClB ) was 22.7 ± 4.19 mL/hr/kg.

Table 4. Summary of Pharmacokinetic Parameters Obtained after a Single Oral Dose of 10 mg Cefpodoxime/kg BW, Administered as a Tablet
PK Parameter Unit Tablet (SD)
AUC0-∞ mcg∙hr/mL 145 (77.6)
AUC0-LOQ mcg∙hr/mL 142 (77.5)
Maximum concentration (Cmax ) mcg/mL 16.4 (11.8)
Terminal plasma elimination half-life (t1/2,z ) hr 5.61 (1.15)
Time of maximum concentration (tmax ) hr 2.21 (0.542)
Mean residence time (MRT0-∞ ) hr 9.21 (1.97)

Microbiology

Like other β-lactam antibiotics, cefpodoxime exerts its inhibitory effect by interfering with bacterial cell wall synthesis. This interference is primarily due to its covalently binding to the penicillin-binding proteins (PBPs) (i.e. transpeptidase and/or carboxypeptidase), which are essential for synthesis of the bacterial cell wall. Therefore, cefpodoxime is bactericidal. Cefpodoxime is stable in the presence of many common β-lactamase enzymes. As a result, many organisms resistant to other β-lactam antibiotics (penicillins and some cephalosporins) due to the production of β-lactamases may be susceptible to cefpodoxime.

Cefpodoxime has a broad spectrum of clinically useful antibacterial activity that includes staphylococci, streptococci, and Gram-negative species (including Pasteurella, Escherichia, and Proteus). The compound is not active against most obligate anaerobes, Pseudomonas spp., or enterococci. The minimum inhibitory concentrations (MICs) for cefpodoxime against Gram-positive and Gram-negative pathogens isolated from canine skin infections (wounds and abscesses) in a 2002 U.S. field study are presented in Table 5. All MICs were determined in accordance with the National Committee for Clinical Laboratory Standards (NCCLS). Appropriate quality control (QC) ranges for in vitro susceptibility testing are presented in Table 6.

Table 5. Cefpodoxime Minimum Inhibitory Concentration Values (mcg/mL) from a 2002 Field Study Evaluating Skin Infections (wounds and abscesses) of Canines in the United States.
Organism * # of Isolates MIC50 MIC90 Range
*
Veterinary specific interpretive criteria have not been established for the above listed canine pathogens by the NCCLS at this time.
No Range, all isolates yielded the same value.
Staphylococcus intermedius 118 0.12 0.50 0.12->32.0
Streptococcus canis (group G, β hemolytic) 33 ≤0.03 ≤0.03 ≤0.03
Escherichia coli 41 0.25 0.50 0.12->32.0
Pasteurella multocida 32 ≤0.03 ≤0.03 ≤0.03-0.12
Proteus mirabilis 14 ≤0.03 0.06 ≤0.03-0.06
Staphylococcus aureus 19 2.0 2.0 0.12-2.0
Table 6. Acceptable Quality Control Ranges for Cefpodoxime
QC ATCC strain KB Disk Diffusion Method Broth Micro-dilution Method
Drug concentration Zone diameter MIC
*
These ranges are for quality control strains used to monitor accuracy of minimum inhibitory concentrations (MICs) of non-fastidious organisms using cation-adjusted Mueller-Hinton agar or broth medium. The dilution range should encompass the QC ranges of these strains in the broth micro-dilution method.
These ranges are for quality control strains used to monitor accuracy of minimum inhibitory concentrations (MICs) of fastidious organisms. When susceptibility testing is performed for Streptococcus canis (group G, β hemolytic), Streptococcus pneumoniae ATCC 49619 should be included as a QC strain in the presence of 5% lysed sheep blood (KB disk diffusion method) or 2.5% lysed horse blood (broth micro-dilution method).
Escherichia coli 25922 10 mcg 23-28 mm * 0.25-1 mcg/mL *
Staphylococcus aureus 25923 10 mcg 19-25 mm *
Staphylococcus aureus 29213 1-8 mcg/mL *
Streptococcus pneumoniae 49619 10 mcg 28-34 mm 0.03-0.12 mcg/mL

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