CLINICAL PHARMACOLOGICAL ASPECTS OF CEFIXIME IN DOGS

The minimal inhibitory concentration (MIC) of cefixime, a new third-ge neration orally administered caphalosporin, was determined for referen ce and clinical isolates from dogs. The MIC of the drug for all but 1 of the 18 Enterobacteriaceae isolates tested, 1 Pasteurella canis, 1 R hodococcus equi, 1 Streptococcus canis, and 1 Streptococcus group G is olate, was less than 1.0 mu g/ml. The MIC for 9 Staphylococcus interme dius isolates ranged from 1.56 to 6.25 mu g/ml and, for 8 Sta aureus i solates, the MIC values ranged from 1.56 to 12.5 mu g/ml. Pseudomonas aeruginosa, Actinomyces sp, and a single Bordetella bronchiseptica iso late were considered resistant to cefixime. Cefixime was administered orally in 2 phases at a standard dosage of 5 mg/kg of body weight to c linically normal adult male and female dogs. In the first phase, the d rug was given once as a capsule and once as a suspension. In the secon d phase, it was administered once per day for 6 consecutive days in ca psule form. Serum drug concentration was determined by use of a microb iological assay, and the following kinetic values were estimated for e ach dog: area under the concentration-time curve, peak serum drug conc entration (C-max), time of C-max, absorption half-life, and eliminatio n half-life (t(1/2el)). The kinetic profile of the drug in serum after oral administration of a single dose of cefixime was similar, with me an C-max values of 3.36 and 4.76 mu g/ml after treatment with the caps ule and suspension, respectively. Quick oral absorption is characteris tic for cefixime in dogs; mean absorption half-life values of 1.3 and 0.58 hours for the capsule and suspension, respectively, were calculat ed. Drug elimination from serum was biphasic, with an initial mean t(1 /2el) of 8.1 to 8.6 hours and a secondary mean t(1/2el) 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. C efixime is extensively bound to canine serum proteins (82 to 92% at co ncentration ranging between 7.5 and 1.5 mu g/ml). Concentration of cef ixime was determined in the uterus, ovaries, and abdominal fat tissues 24 hours after single-dose treatment and 24 hours after the sixth tre atment. Tissue drug distribution was limited after administration of t he single dose, but improved after the sixth dose. The in vitro antiba cterial activity of the drug and its pharmacokinetic properties warran t assessing its clinical and bacteriologic efficacy as a longterm once -daily orally administered treatment for common bacterial infections i n dogs.