Nonlinear toxicokinetics of enrofloxacin in rats

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Abstract
The dose-dependent toxicokinetics of enrofloxacin were studied by administering various single subcutaneous doses (5, 10, 20, 40, 70, 100, 150, 200, 300 and 400 mg/kg) in male Sprague-Dawley rats. The blood samples were collected from the tail veins, and the plasma concentration of enrofloxacin was determined by an HPLC-fluorescence detection (FLD) method. The time-concentration profiles of enrofloxacin were well fitted by an one-compartmental model with first order elimination. The absorption half-lives (t1/2abs) ranged from 0.2–0.8 h, and the mean time to maximum plasma concentration (Tmax) ranged from 0.6–1.8 h. On the other hand, marked disproportionate increases of the area under the curve (AUC) and elimination half-lives (t1/2) were observed from the increase of the doses. This result indicates that the elimination of enrofloxacin has nonlinear pharmacokinetic properties with increasing doses. Therefore, we need to take into consideration the possible occurrence of side effects resulting from greater systemic exposure from high dose therapies.

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