Pharmacokinetics and milk penetration of difloxacin after intravenous, subcutaneous and intramuscular administration to lactating goats

Abstract

The single-dose disposition kinetics of difloxacin were determined in clinically normal lactating goats (n = 6) after intravenous (i.v.), subcutaneous (s.c.) and intramuscular (i.m.) administration of 5 mg/kg. Difloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analysed by compartmental and noncompartmental kinetic methods. Steady-state volume of distribution (V(ss)) and total body clearance (Cl) of difloxacin after i.v. administration were estimated to be 1.16 +/- 0.26 L/kg and 0.32 +/- 0.05 L/h x kg respectively. Following s.c. and i.m. administration difloxacin achieved maximum plasma concentrations of 1.33 +/- 0.25 and 1.97 +/- 0.40 mg/L at 3.37 +/- 0.36 and 1.79 +/- 1.14 h respectively. The absolute bioavailabilities after s.c. and i.m. routes were 90.16 +/- 11.99% and 106.79 +/- 13.95% respectively. Difloxacin penetration from the blood into the milk was extensive and rapid, and the drug was detected for 36 h after i.v. and s.c. dosing, and for 72 h after i.m. administration.

Allometric scaling of marbofloxacin, moxifloxacin, danofloxacin and difloxacin pharmacokinetics: a retrospective analysis

“…Similar results also occurred when difloxacin and moxifloxacin were administered to lactating goats (Fernandez‐Varon et al. , 2005a; Marin et al. , 2007a).…”

“…The penetration of danofloxacin from the blood of cows into milk was rapid and extensive with concentrations in the milk exceeding those in the serum (Shem-Tov et al, 1998). Similar results also occurred when difloxacin and moxifloxacin were administered to lactating goats (Fernandez-Varon et al, 2005a;Marin et al, 2007a). Marbofloxacin penetration into milk was rapid and extensive with milk concentrations exceeding those in serum 2 h after administration to lactating cows and ewes (Shem-Tov et al, 1997).…”

“…Bioavailability for difloxacin was between 86% and 99% in calves, rabbits, pigs and chickens (Inui et al. , 1998; Ismail & El‐Kattan, 2007; Marin et al. , 2007a).…”

“…Although there is considerable individual variation among the different compounds and in different species, generally FQs are rapidly absorbed following oral administration in monogastric species. Bioavailability for difloxacin was between 86% and 99% in calves, rabbits, pigs and chickens (Inui et al, 1998;Ismail & El-Kattan, 2007;Marin et al, 2007a). Danofloxacin had an oral bioavailability of 99% and 100% in chickens and goats (Knoll et al, 1999;Aliabadi & Lees, 2001).…”

Comparative pharmacokinetics of intravenous cephalexin in pregnant, lactating, and nonpregnant, nonlactating goats

“…, 1997; Ambros et al. , 2007; Marín et al. , 2007), thus, therapeutic efficacy may become unpredictable.…”