Pharmacokinetics of difloxacin in Sichuan Shelducks after single or multiple dosing

This is the authors' abstract. We don't add key points for this paper.

This study evaluated both single and multiple dosing regimens of difloxacin administered via different routes to Sichuan Shelducks: single intramuscular ( sIM ), intravenous ( sIV ), oral gavage ( sPO ), and multiple intramuscular ( mIM ) and oral gavage ( mPO ) administrations. The sIV, sPO, and sIM groups received a single dose of difloxacin at 10 mg/kg body weight ( BW ). The mPO and mIM groups received multiple doses of 10 mg/kg BW at 12-hour intervals: the mPO group received 10 oral doses, and the mIM group received 6 intramuscular doses. Blood samples were collected at various time points from 0 to 48 hours, and plasma concentrations of difloxacin were analyzed using a validated high-performance liquid chromatography ( HPLC ) method. Pharmacokinetic parameters were calculated using Phoenix software and non-compartmental analysis ( NCA ). The peak plasma concentration ( C max ) values were 2.05 ± 0.60, 2.26 ± 0.36, 2.81 ± 0.92, and 3.42 ± 0.59 μg/mL for the sPO, sIM, mPO, and mIM groups, respectively, with corresponding peak time ( t max ) of 0.75 ± 0.17, 0.77 ± 0.26, 0.96 ± 0.61, and 0.65 ± 0.33 hours. The PO and IM bioavailability ( F ) after single administration were 96.00 % ± 22.03 % and 87.62 % ± 9.81 %, respectively. Following single IV administration, difloxacin exhibited extensive distribution, with a volume of distribution ( V Z ) of 6.12 ± 3.59 L/kg and a steady-state volume of distribution ( V SS ) of 3.18 ± 1.09 L/kg. Difloxacin was eliminated slowly, with terminal half-lives ( t 1/2λz ) of 10.77 ± 1.78, 4.53 ± 4.44, 4.53 ± 2.97, 6.00 ± 2.00, and 5.33 ± 4.35 hours in the sPO, sIM, sIV, mPO, and mIM groups, respectively. Based on the AUC/MIC ratios, the current single IV and PO dosing regimens, as well as the multiple IM and PO regimens, appear effective against pathogens with MIC values ≤ 0.1 μg/mL. However, the single IM dose of 10 mg/kg BW may be inadequate for treating infections caused by organisms with MIC values > 0.1 μg/mL.