Pharmacokinetics and tissue residues of pefloxacin and its metabolite norfloxacin in broiler chickens

Abstract

1.	The pharmacokinetics of pefloxacin and its active metabolite norfloxacin were investigated in chickens after a single oral administration of pefloxacin at a dosage of 10 mg/kg. To characterise the residue pattern, another group of chickens was given 10 mg of pefloxacin/kg body once daily for 4 d by oral route; the tissue concentrations of pefloxacin and norfloxacin were determined at 1, 5 and 10 d after the last administration of the drug.
2.	The concentrations of pefloxacin and norfloxacin in plasma and tissues were determined by HPLC assay. The limit of detection for pefloxacin and norfloxacin was 0·03 µg/ml in plasma or µg/g in tissue.
3.	The plasma concentration–time data for pefloxacin and norfloxacin were characteristic of a one-compartment open model. The elimination half-life, maximum plasma drug concentration, time to reach maximum plasma drug concentration and mean residence time of pefloxacin were 8·74 ± 1·48 h, 3·78 ± 0·23 µg/ml, 3·33 ± 0·21 h and 14·32 ± 1·94 h, respectively, whereas the respective values of these variables for norfloxacin were 5·66 ± 0·81 h, 0·80 ± 0·07 µg/ml, 3·67 ± 0·21 h and 14·44 ± 0·97 h.
4.	Pefloxacin was metabolised to norfloxacin to the extent of 22%.
5.	The concentrations of pefloxacin (µg/g) 24 h after the fourth dose of the drug declined in the following order: liver (3·20 ± 0·40) > muscle (1·42 ± 0·18) > kidney (0·69 ± 0·04) > skin and fat (0·06 ± 0·02). Norfloxacin was also detectable in all the tissues analysed except muscle. No drug and/or its metabolite was detectable in tissues except skin and fat 5 d after the last administration. The concentrations of pefloxacin and norfloxacin in skin and fat 10 d after the last dose of pefloxacin were 0·04 ± 0·02 and 0·03 ± 0·01 µg/g, respectively.

Acknowledgements

The authors wish to acknowledge M/s Wockhardt, Mumbai, India and M/s Cipla Pharmaeuticals Pvt Limited, Mumbai, India for their generous supply of pefloxacin and norfloxacin used in the present study. They also express their gratitude to the Director, Indian Veterinary Research Institute, Izatnagar and Director, Central Avian Research Institute, Izatnagar for providing necessary facilities.