Influence of E. coli lipopolysaccharide induced fever on the plasma kinetics of cefepime in cross-bred calves

Abstract

The pharmacokinetic behavior of cefepime was studied in healthy and febrile cross-bred calves after single intravenous administration (10 mg/kg). The fever was induced with E. coli lipopolysaccharide (1 microg/kg, IV). The drug concentration in plasma was detected by microbiological assay method using E. coli (MTCC 739) test organism. Pharmacokinetic analysis of disposition data indicated that intravenous administration data were best described by 2 compartment open model. At 1 min the concentration of cefepime in healthy and febrile animals were 55.3 +/- 0.54 microg/ml and 50.0 +/- 0.48 microg/ml, respectively and drug was detected up to 12 h. The elimination half-life of cefepime was increased from 1.26 +/- 0.01 h in healthy animals to 1.62 +/- 0.09 h in febrile animals. Drug distribution was altered by fever as febrile animals showed volume of distribution (0.27 +/- 0.02 L/kg) higher than normal animal (0.19 +/- 0.01 L/kg). Total body clearances in healthy and febrile animals were 104.4 +/- 2.70 and 114.2 +/- 1.20 ml/kg/h, respectively. To maintain minimum therapeutic concentration of 1 mug/ml, a satisfactory dosage regimen of cefepime in healthy and febrile cross-bred calves would be 15.5 mg/kg and 8.2 mg/kg body weight, respectively, to be repeated at 8 h intervals. The T>MIC values (8 h) of cefepime suggested that this agent is clinically effective in the treatment of various infections.

Pharmacokinetic Studies Of Ceftiofur (Ceftiprima In Calves)

“…(Sudamrao, 2015)and sheep by the dose of 1.1mg ceftiofur/k.g .b.wt. (0.10h, Craigmill et al,1997).While longer half-life of distribution of ceftiofur was recorded of ceftiofur cattle (0.462h; Tohamy, 2008),camel (0.48h; Goudah, 2007), bull calves 6 and 9 months (0.88, 0.74h; Brown et al,1996), lactating andnonlactating goats (0.69h, 0.8h; Courtin et al, 1997), sheep (4.8h;Craigmill et al,1997).The differences between the value systems calculated for pharmacokinetic parameters can be directly linked to the species of animal, formulations of the drug used, the sex, size or age of the animals, discrepancies in deposits of fatty tissue between breeds or species of animals , and even interindividual variations, as well as the drug analysis method (Riond et al, 1989).This result of halflife of the distribution to.5(α), compared to other cephalosporins, is almost comparable to that earlier reported in cefquinome in yellow cattle (0.29 h, Shan et al,2013),cefepime in goats (0.20 h;El-Hewaity, 2014),cefepime in sheep (0.2h, Patel et al,2010),cefepime in calves (0.2 h;0.25h, Ismail, 2005b;Pawar and Sharma 2008),cefepime in ewes (0.18 h, Ismail,2005a)and cefepime in buffalo calves (0.18 h, Joshi and Sharma 2007).…”

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

“…Abundant intravenous fluid therapies that increase extracellular compartment fluid may cause a significant increase in distribution [ 40 ]. Elevated distribution volumes of CS and cefepime have been shown in experimentally infected pigs and calves [ 32 , 47 ]. Combination therapies including vasopressor drugs and abundant intravenous fluid therapies may lead to an increase in distribution of CS by causing rapid transfer of the drug into the tissues and prolonging elimination in endotoxemic calves.…”

Bioavailability Study of Cefepime After Intravenous and Intramuscular Administration in Normal Broiler Chickens

“…The bioavailability (F%) of cefepime in normal chickens was (104.3±2.34%) which was agrees with those reported in cefquinome in cattle 104±7.13 %, (Shan, et al, 2013) and sheep 103±8% (Patel, et al, 2010) but higher than that reported in cefepime in goats 86.45 ±17.39; 69±6; 92.66% (Bhavsar et al, 2008;Prawez, et al, 2010;El-Hewaity, 2014) respectiveely, calves 95.3±10.5; 95.7±7.44%, (Ismail, 2005b;Joshi and Sharma 2007) respectively, bull camels 91.7± 12.35% (Goudah, et al, 2009), and ewes 86.8±7.5 % (Ismail, 2005a). Following intravenous administration, the distribution half-life (t1/2α) is closely similar to cefepime that previously reported in goats 0.20 ± 0.004; 0.20 ± 0.002 h, (Bhavsar, et al, 2008;El-Hewaity, 2014), buffalo calves 0.18 ± 0.05 h (Joshi and Sharma 2007), sheep 0.2 ± 0.02 h (Patel, et al, 2010), calves 0.2 ± 0.02 h; 0.25 ± 0.07 h, (Ismail, 2005b;Pawar and Sharma 2008) and ewes 0.18 ± 0.008 h (Ismail, 2005a). Longer half-life of distribution was recorded for cefepime in bull camels 0.30 ± 0.05h, (Goudah, et al, 2009), horses 0.39 ± 0.18 h (Guglick, et al, 1998) and neonatal foals and adult dogs 0.30 ± 0.16 h; 0.39 ± 0.21 h, (Gardner and Papich 2001) respectively.…”

“…The peptidoglycan layer is important for cell wall structural integrity. The pharmacokinetics of cefepime has been extensively investigated in various animal species as rats and monkeys (Forgue et al, 1987), rabbits (Goudah et al, 2006;Abd El-Aty et al, 2007;Rule et al, 2010), horses (Guglick et al, 1998), foals and dogs (Gardner and Papich, 2001), cow calves (Ismail, 2005b;Patel et al, 2006;Pawar and Sharma, 2008;Patel et al, 2012), ewe (Ismail, 2005a ), goats (El-Rabbat et al, 2010;Rule et al, 2001;Bhavsar et al, 2008;Prawez et al, 2010;El-Hewaity, 2014), bull camels (Goudah et al, 2009), sheep (Patel et al, 2010) and buffalo calves (Joshi and Sharma 2007;Joshi and Sharma 2009). Currently, there are no available data on the pharmacokinetics of cefepime in broiler chickens.…”