Pharmacokinetics of ceftiofur in healthy and lipopolysaccharide-induced endotoxemic newborn calves treated with single and combined therapy

Abstract

The aim of this research was to compare plasma pharmacokinetics of ceftiofur sodium (CS) in healthy calves, and in calves with experimentally induced endotoxemia. Six calves received CS (2.2 mg/kg, IM) 2 hr after intravenous administration of 0.9% NaCl (Ceft group). After a washout period, the same 6 calves received CS 2 hr after intravenous injection of lipopolysaccharide (LPS+Ceft group). Another group of 6 calves received a combination of drug therapies that included CS 2 hr after administration of 0.9% NaCl (Comb group). A third group of 6 calves received the same combination therapy regimen 2 hr after intravenous injection of lipopolysaccharide (LPS+Comb group). Plasma concentrations of CS and all desfuroylceftiofur-related metabolites were determined using HPLC, and its pharmacokinetic properties were determined based on a two-compartment model. The peak concentration of CS in the LPS+Comb group occurred the earliest, and the clearance rate of CS was the highest in the Comb and LPS+Comb groups (P<0.05). The elimination half-life of CS in the LPS+Ceft group was longer than that in the Ceft and Comb groups (P<0.05). The results of this study indicate that combined therapies and endotoxemic status may alter the plasma pharmacokinetics of CS in calves.

Pharmacokinetic Studies Of Ceftiofur (Ceftiprima In Calves)

“…Ceftiofur reached a maximum serum concentration after (2.48±0.07h) this result is similar to ceftiofur reported in cattle and water buffalo (2.00 and 2.87h , Nie et al,2015 andGorden et al,2015). The present result is nearly similar to the results in calves (1.82 and 1.5h;Halsteadet al,1992 and Altan et al,2017).however disagreed with those stated in sheep (0.81h, Craigmill et al,1997), goats (1.17h, Courtin et al, 1997), camel (1.22h, Goudah, 2007), buffalo calves (0.33h, Sudamrao,2015) and cattle (0.67h, Hornish and Kotarski 2002). After comparison to other cephalosporin, the time studied to reach the maximum serum concentration (Tmax) was agreed with those reported in cefqinome in broiler chicken (2.8h,El-Mahdy et al, 2015) The mean peak ceftiofur serum concentration (Cmax) was (6.50±0.12 μg/ml) after intramuscular administration of 2.2 mg ceftiofur /kg.bw these values are consistence with those in water buffalo (6.2μg/ml, Nie et al,2015),buffalo calves (6.6μg/ml ,Sudamrao, 2015), calves (7.73 μg/ml, Altan et al,2017), sheep (7.13μg/ml, Craigmill et al,1997) and cows (7.8μg/ml, Tohamy, 2008).…”

“…The longer elimination time(t0.5(el)) in calves may be largely related to less maturation of eliminating organs and/or elimination processes of ceftiofur and its metabolite particularly in comparison to adult and old animals of various species (Brown et al,1996). On the opposite, lower elimination time (19.9 h) in calves (Altan et al,2017) relative to the current inquiry may be owing to varieties in the enzymatically catalyzed metabolism and ceftiofur renal excretion, including effective renal secretion through organic acid transporters, and also glomerular filtration in such animals (Brown et al, 1996).…”

“…All standard solutions were kept at +4 0 C. Functioning solutions of Ceftiofur used to confound plasma were arranged at 10.00, 1.00 and 0.10 µg/ml concentrations from standard solutions by attenuating with deionized water. Standard concentrations were gotten by extra attenuation in drug free normal calves serum to attain concentrations 0.05, 0.10, 0.25, 0.50, 1.00, 5.00, 10.0 and 25.0 µg/ml for creation of standard curve of ceftiofur according to (Altan et al, 2017) . Drug free normal calves serum was pointed with ceftiofur from the formerly prepared concentration.…”

“…Drug free normal calves serum was pointed with ceftiofur from the formerly prepared concentration. Ceftiofur was take out according to (Altan et al, 2017). In an eppindorf tube, Inpassing, nearly 200 μl of each serum sample was taken and 200 μl of methanol was added then samples were vortexed for 30 sec.…”

Effect of supportive therapy on the pharmacokinetics of intravenous marbofloxacin in endotoxemic sheep

“…In the present study, increased AUC 0–∞ of marbofloxacin in the MBX + ST + LPS group may have resulted from changes in plasma concentrations and plasma concentration–time curve. Previous studies have reported that LPS‐induced endotoxemia causes an increase in AUC of the drugs (Altan et al, 2017; Elmas et al, 2006; Waxman et al, 2003).…”