Influence of ruminal distribution on norfloxacin pharmacokinetics in adult sheep
2001
González, F. | San Andres, M.I. | Nieto, J. | San Andres, M.D. | Waxman, S. | Vicente, M.L. | Lucas, J.J. | Rodriguez, C.
Norfloxacin (NF) ruminal distribution after intravenous (i.v.), intramuscular (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. administrations between 4 and 48 h in all animals studied. The experimental distribution ratios after i.v. and i.m. administration expressed as area under the concentration-time curve ratios AUCrumen/AUCplasma were 0.24 and 0.39, respectively, and thus lower than corresponding predicted value of 5.06. Apparently, drug persisted in the rumen content longer than in plasma. The experimental mean residence time ratios MRTrumen/MRTplasma after i.v. and i.m. administrations were 2.33 and 1.66, respectively. After p.o. administration, NF concentrations in the rumen content were extremely high compared with the respective plasma concentrations, resulting in mean peak concentrations ratio Cmax-rumen/Cmax-plasma of 383.66 and AUCrumen/AUCplasma experimental ratio of 402.32. This value was considerably higher (approximately equal to 79 fold) than the predicted distribution ratio of 5.06. Our results suggest that the limited p.o. bioavailability of NF in ruminants could not be attributed to ruminal degradation.
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