Influence of ruminal distribution on norfloxacin pharmacokinetics in adultsheep

Norfloxacin (NF) ruminal distribution after intravenous (i.v.), intramuscul ar (i.m.) and oral (p.o.) administration was determined in order to assess the influence of the rumen on the pharmacokinetic behaviour of NF in sheep. Norfloxacin concentrations in rumen were detected after i.v. and i.m. admi nistrations between 4 and 48 h in all animals studied. The experimental dis tribution ratios after i.v. and i.m. administration expressed as area under the concentration-time curve ratios AUC(rumen)/AUC(plasma) were 0.24 and 0 .39, respectively, and thus lower than corresponding predicted value of 5.0 6. Apparently, drug persisted in the rumen content longer than in plasma. T he experimental mean residence time ratios MRTrumen/MRTplasma after i.v. an d i.m. administrations were 2.33 and 1.66, respectively. After p.o. adminis tration, NF concentrations in the rumen content were extremely high compare d with the respective plasma concentrations, resulting in mean peak concent rations ratio Cmax-rumen/Cmax-plasma of 383.66 and AUC(rumen)/AUC(plasma) e xperimental ratio of 402.32. This value was considerably higher (approximat e to 79 fold) than the predicted distribution ratio of 5.06. Our results su ggest that the limited pro. bioavailability of NF in ruminants could not be attributed to ruminal degradation.