PHARMACOKINETICS AND TISSUE RESIDUES OF NORFLOXACIN AND ITS N-DESETHYL-METABOLITES AND ORE-METABOLITES IN HEALTHY PIGS

The pharmacokinetic properties of norfloxacin were determined in healt hy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosag e of 8 mg/kg body weight. After i.m. and i.v. administration, the plas ma concentration-time graph was characteristic of a two-compartment op en model. After single i.m. administration, norfloxacin was absorbed r apidly, with a t(max) of 1.46 +/- 0.06 h. The elimination half-life (t (1/2 beta)) and the mean residence time of norfloxacin in plasma were 4.99 +/- 0.28 and 6.05 +/- 0.22 h, respectively, after i.m. administra tion and 3.65 +/- 0.16 and 3.34 +/- 0.16 h, respectively, after i.v. a dministration. Intramuscular bioavailability was found to be 53.7 +/- 4.4%. Plasma concentrations greater than 0.2 mu g/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma con centration was 1.11 +/- 0.03 mu g/mL. statistically significant differ ences between the two routes of administration were found for the half -lives of both distribution and elimination phases(t(1/2 alpha), t(1/2 beta)) and apparent volume of distribution (V-d(area)). In pigs, norf loxacin was mainly converted to desethylenenorfloxacin and oxonorfloxa cin, Considerable tissue concentrations of norfloxacin, desethylenenor floxacin, and oxonorfloxacin were found when norfloxacin was administe red intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.01 5 and 0.017 mu g/g on day 12 after the end of dosing.