Pharmacokinetics of difloxacin in pigs and broilers following intravenous, intramuscular, and oral single‐dose applications

Abstract

Pharmacokinetics of difloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of five (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analyzed by a compartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t(1/2beta)) were 17.14 +/- 4.14, 25.79 +/- 8.10, 16.67 +/- 4.04 (pigs) and 6.11 +/- 1.50, 5.64 +/- 0.74, 8.20 +/- 3.12 h (broilers), respectively. After single i.m. and p.o. administration, difloxacin was rapidly absorbed, with peak plasma concentrations (C(max)) of 1.77 +/- 0.66, 2.29 +/- 0.85 (pigs) and 2.51 +/- 0.36, 1.00 +/- 0.21 microg/mL (broilers) attained at t(max) of 1.29 +/- 0.26, 1.41 +/- 0.88 (pigs) and 0.86 +/- 0.4, 4.34 +/- 2.40 h (broilers), respectively. Bioavailabilities (F) were (95.3 +/- 28.9)% and (105.7 +/- 37.1)% (pigs) and (77.0 +/- 11.8)% and (54.2 +/- 12.6)% (broilers) after i.m. and p.o. doses, respectively. Apparent distribution volumes(V(d(area))) of 4.91 +/- 1.88 and 3.10 +/- 0.67 L/kg and total body clearances(Cl(B)) of 0.20 +/- 0.06 and 0.37 +/- 0.10 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), the half-lives of both absorption and distribution(t(1/2ka), t(1/2alpha)) were also determined. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 5 mg/kg given intramuscularly every 24 h in pigs, or administered orally every 24 h at the dosage of 10 mg/kg in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC(90) are <0.25 microg/mL and <0.1 microg/mL respectively.

Pharmacokinetics and milk penetration of difloxacin after a long-acting formulation for subcutaneous administration to lactating goats

“…Difloxacin was well absorbed following SC and P407 administration, with absolute bioavailabilities (F) of 81.74 and 72.58%, respectively. Similar high values have been obtained for difloxacin in rabbits, goats, lambs, pigs, and broilers (Fernández-Varón et al, 2006;Marín et al, 2007a;Ding et al, 2008;Goudah and Mouneir, 2008).…”

Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination

“…This finding indicates that, within the range of doses examined, the high absolute bioavailability of marbofloxacin injectable solution is not affected by the drug concentration (cross-study comparison), dose (within and between study comparison) or by the injection volume (within study comparison). A high absolute bioavailability of about 95% was also obtained in pigs following intramuscular administration of difloxacin ( Ding et al , 2008 ). Somewhat lower values were obtained following intramuscular administration of other fluoroquinolones: 75% for enrofloxacin ( Anadón et al ., 1999 ), 76% for danofloxacin ( Mann & Frame, 1992 ) and 54% for norfloxacin ( Anadón et al ., 1995 ).…”

“…(2010) were even younger than the 12-week-old animals in the present work. The clearance of marbofloxacin is lower than that estimated for enrofloxacin (0.1–0.45 L/h·kg, Anadón et al ., 1999 ; Post et al , 2002 , 2003 ), difloxacin (0.16 L/h·kg, Ding et al , 2008 ), danofloxacin (0.63 L/h·kg, Mann & Frame, 1992 ) and norfloxacin (0.66 L/h·kg, Anadón et al ., 1995 ).…”

Using In Vitro Dynamic Models To Evaluate Fluoroquinolone Activity against Emergence of Resistant Salmonella enterica Serovar Typhimurium

“…Single daily doses of the three FQs for 3 consecutive days with simulated half-lives (t 1/2 ) consistent with those reported in pigs were used: 12.5 h for DIF (33,34), 10.6 h for ENR (35,36) and 8 h for MAR (37). The doses were selected to include the achievable area under the curve (AUC) and maximum plasma concentration (C max ) over a 24-h dosing interval at the recommended clinical doses (1 to 5 mg/kg of body weight for DIF, 2.5 to 5 mg/kg for ENR, and 2 mg/kg for MAR) in pigs.…”