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.