Clinical pharmacologic aspects of cefixime in dogs

The minimal inhibitory concentration (MIC) of cefixime, a new third-generation orally administered cephalosporin, was determined for reference and clinical isolates from dogs. The MIC of the drug for all but 1 of the 18 Enterobacteriaceae isolates tested, 1 Pasteurella canis, 1 Rhodococcus equi, 1 Streptococcus canis, and 1 Streptococcus group C isolate, was less than 1.0 μg/ml. The MIC for 9 Staphylococcus intermedius isolates ranged from 1.56 to 6.25 μg/ml and, for 8 Sta aureus isolates, the MIC values ranged from 1.56 to 12.5 μg/ml. Pseudomonas aeruginosa, Actinomyces sp, and a single Bordetella bronchiseptica isolate were considered resistant to cefixime. Cefixime was administered orally in 2 phases at a standard dosage of 5 mg/kg of body weight to clinically normal adult male and female dogs. In the first phase, the drug was given once as a capsule and once as a suspension. In the second phase, it was administered once per day for 6 consecutive days in capsule form. Serum drug concentration was determined by use of a microbiological assay, and the following kinetic values were estimated for each dog: area under the concentration-time curve, peak serum drug concentration (C(max)), time of C(max), absorption half-life, and elimination half-life (t( 1/2 el)). The kinetic profile of the drug in serum after oral administration of a single dose of cefixime was similar, with mean C(max) values of 3.36 and 4.76 μg/ml after treatment with the capsule and suspension, respectively. Quick oral absorption is characteristic for cefixime in dogs; mean absorption half-life values of 1.3 and 0.58 hours for the capsule and suspension, respectively, were calculated. Drug elimination from serum was biphasic, with an initial mean t( 1/2 el) of 8.1 to 8.6 hours and a secondary mean t( 1/2 el) of 11.7 to 14.5 hours. In the trial involving once daily treatment for 6 days, serum drug concentration after the sixth dose was significantly (P < 0.05) higher than that after the first dose, indicating drug accumulation. Cefixime is extensively bound to canine serum proteins (82 to 92% at concentration ranging between 7.5 and 1.5 μg/ml). Concentration of cefixime was determined in the uterus, ovaries, and abdominal fat tissues 24 hours after single-dose treatment and 24 hours after the sixth treatment. Tissue drug distribution was limited after administration of the single dose, but improved after the sixth dose. The in vitro antibacterial activity of the drug and its pharmacokinetic properties warrant assessing its clinical and bacteriologic efficacy as a long-term once-daily orally administered treatment for common bacterial infections in dogs.