Influence of Escherichia coli endotoxin-induced fever on the pharmacokinetic behavior of marbofloxacin after intravenous administration in goats

The pharmacokinetic behavior of marbofloxacin was studied in seven healthy goats and in the same goats with induced fever after single-dose intravenous (i.v.) administration of 2 mg/kg b.w. Fever was induced by the administration of Escherichia coli endotoxin. Drug concentration in plasma was determined by high-performance liquid chromatography (HPLC). Drug distribution was somehow altered by fever as febrile goats showed a volume of distribution at steady-state (V-ss=0.72+/-0.15 L/kg) lower than normal goats (V-ss=1.19+/-0.33 L/kg). The elimination of the drug was also modified. Total plasma clearance (Cl ) decreased from 0.24+/-0.12 L/kg/h in healthy animals to 0.13+/-0.05 L/kg/h in animals with endotoxin-induced fever, which is related to an increase in the area under the plasma concentration-time curve (AUC ). Consequently, mean residence time (MRT ) was also slightly increased in sick animals (MRT=5.28+/-00.99 and 6.09+/-01.45 h, in healthy and febrile animals, respectively).