Influence of endotoxin induced fever on the pharmacokinetics of intramuscularly administered cefepime in rabbits.
This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 x 10(8) colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1 degrees C. There was a significant reduction in the elimination halflife by 21.8 % in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9 %, the mean residence time by 19.9 %, the area under the plasmaconcentration-time curve by 53.6 % and the area under the moment curve by 62.3 %. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits.
Goudah
Ayman
A
Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 12211-Giza, Egypt.
Mouneir
Samar M
SM
Shim
Jae-Han
JH
Abd El-Aty
A M
AM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004731:Endotoxins / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000503:physiopathology; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D006207:Half-Life; D007273:Injections, Intramuscular; D008297:Male; D011817:Rabbits
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004731:Endotoxins; D000077723:Cefepime