Cefpodoxime proxetil (Simplicef, pfizerah.com) is a third-generation cephalosporin approved for use in dogs. Cephalexin is a first-generation cephalosporin that is used in an extralabel manner in dogs. Both are successfully used for treatment of bacterial infections in dogs. This study looked at the effect of protein binding on the pharmacokinetics and the distribution of cephalexin and cefpodoxime from tissues to interstitial fluid (ISF) in dogs and also compared the observed drug concentrations in the MIC90 (minimum inhibitory concentration) against 2 common pathogens. There is evidence that antimicrobial concentrations at the target site (such as ISF) are responsible for antimicrobial effects and more likely to predict therapeutic efficacy than are plasma concentrations. This was a 2-period, 2-treatment crossover design using 6 adult dogs with a 7-day washout period between treatments. Dosages of 9.6 mg/kg cefpodoxime proxetil or 25 mg/kg cephalexin were administered orally. Blood and ISF samples were collected for a 24-hour period. Additional samples were collected at 32 and 48 hours when cefpodoxime was administered. The tissue concentration of protein-unbound cefpodoxime was similar to the protein-unbound plasma concentration. Cephalexin did not remain in the tissue as long as cefpodoxime and never reached equilibrium. The mean protein-unbound drug ISF concentrations of cefpodoxime exceeded the MIC90 for Staphylococcus pseudintermedius and Escherichia coli for about 24 hours. Cephalexin concentration in ISF exceeded the MIC90 for S pseudintermedius for approximately 12 hours but did not exceed the MIC90 for E coli. Three properties of cefpodoxime favor its use for the treatment of antimicrobial infections: high protein binding, high antimicrobial activity, and its property as a time-dependent antimicrobial. Study supported in part by Pfizer Animal Health

Commentary: This study reminds us about the importance of the ability of antimicrobials to efficiently travel to the site of infection, and that plasma levels may not accurately predict drug efficacy. This is the first published study comparing the tissue levels of these 2 drugs and seems to agree with earlier efficacy reports. The long plasma and tissue cefpodoxime duration may allow once-daily administration, which may improve compliance, an important consideration in many patients.—Patricia Thomblison, DVM, MS

Pharmacokinetics, protein binding, and tissue distribution of orally administered cefpodoxime proxetil and cephalexin in dogs. Papich MG, Davis JL, Floerchinger AM. AM J VET RES 71:1484-1491, 2010.