The pharmacokinetic features of doxycycline (5mg/kg) were investigated after single intravenous (IV) injection and oral administration either alone or co-administered with ketoprofen (3mg/kg) and under febrile condition (Escherichia coli induced fever) in rabbits. The pharmacokinetic parameters of doxycycline were determined by the non-compartmental model with WinNonlin 4.1 software. Following oral treatment with doxycycline alone, the bioavailability was 97.82%. The value of the area under plasma concentration- time curve from 0 to infinite (AUC0-∞) was significantly lower in febrile rabbits ( 101.42 ± 17.73 µg*h/ml) than healthy rabbits received doxycycline alone orally ( 169.37 ± 10.35 µg*h/ml), whereas total body clearance was significantly higher in febrile rabbits than healthy ones administered doxycycline alone. These changes in pharmacokinetic parameters may influence the dose-schedule of doxycycline when used in febrile conditions. A 12-h oral dosing interval of 5 mg/kg is recommended to be effective against rabbit pathogens. In contrast, the pharmacokinetic parameters of doxycycline following concurrent administration with ketoprofen were not significantly varied compared to those after its administration alone. This suggests no need for changing the dose regimen of doxycycline when administered simultaneously with ketoprofen and thus both drugs can be administered concomitantly for management of infection and painful conditions in rabbits.

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