PHARMACOKINETIC VARIATIONS OF OFLOXACIN IN NORMAL AND FEBRILE RABBITS

The influence of experimentally Escherichia coli-induced fever (EEIF) on the pharmacokinetics of ofloxacin was evaluated. Ofloxacin was administered @ 20 mg.kg-1 body weight intravenously to a group of eight healthy rabbits and compared these results to values in same eight rabbits with EEIF. Pharmacokinetic parameters of ofloxacin in normal and febrile rabbits were determined by using two compartment open kinetic model. Peak plasma level (Cmax) and area under the plasma concentration-time curve (AUC0-α) in normal and febrile rabbits did not differ (P>0.05). However, area under first moment of plasma concentration-time curve (AUMC0-α) in febrile rabbits was significantly (P<0.05) higher than that in normal rabbits. Mean values for elimination rate constant (Ke), elimination half life (t1/2β) and apparent volume of distribution (Vd) were significantly (P<0.05) lower in febrile rabbits compared to normal rabbits, while mean residence time (MRT) and total body clearance (Cl) of ofloxacin did not show any significant difference in the normal and febrile rabbits. Clinical significance of the above results can be related to the changes in the volume of distribution and elimination half life that illustrates an altered steady state in febrile condition; hence, the need for an adjustment of dosage regimen in EEIF is required