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  • Author or Editor: Amanda M. Floerchinger x
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Abstract

Objective—To determine the effect of protein binding on the pharmacokinetics and distribution from plasma to interstitial fluid (ISF) of cephalexin and cefpodoxime proxetil in dogs.

Animals—6 healthy dogs.

Procedures—In a crossover study design, 25 mg of cephalexin/kg or 9.6 mg of cefpodoxime/kg was administered orally. Blood samples were collected before (time 0) and 0.33, 0.66, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours after treatment. An ultrafiltration device was used in vivo to collect ISF at 0, 2, 4, 6, 8, 10, 12, 16, and 24 hours. Plasma and ISF concentrations were analyzed with high-pressure liquid chromatography. Plasma protein binding was measured by use of a microcentrifugation technique.

Results—Mean plasma protein binding for cefpodoxime and cephalexin was 82.6% and 20.8%, respectively. Mean ± SD values for cephalexin in plasma were determined for peak plasma concentration (Cmax, 31.5 ± 11.5 μg/mL), area under the time-concentration curve (AUC, 155.6 ± 29.5 μg•h/mL), and terminal half-life (T½, 4.7 ± 1.2 hours); corresponding values in ISF were 16.3 ± 5.8 μg/mL, 878 ± 21.0 μg•h/mL, and 3.2 ± 0.6 hours, respectively. Mean ± SD values for cefpodoxime in plasma were 33.0 ± 6.9 μg/mL (Cmax), 282.8 ± 44.0 μg•h/mL (AUC), and 5.7 ± 0.9 hours (T1/2); corresponding values in ISF were 4.3 ± 2.0 μg/mL, 575 ± 174 μg•h/mL, and 10.4 ± 3.3 hours, respectively.

Conclusions and Clinical Relevance—Tissue concentration of protein-unbound cefpodoxime was similar to that of the protein-unbound plasma concentration. Cefpodoxime remained in tissues longer than did cephalexin.

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in American Journal of Veterinary Research