caa a22 4500 463236874 CHVBK 20180405153300.0 cr unu---uuuuu 170326e20070101xx s 000 0 eng 10.1007/s11259-006-3405-2 doi (NATIONALLICENCE)springer-10.1007/s11259-006-3405-2 Acute-phase Response Alters the Disposition Kinetics of Cefepime following Intravenous Administration to Rabbits [Elektronische Daten] [A. El-Aty, A. Goudah, S. Mouneir, Y. Sunwoo, J. Jang, J. Shin, J. Shim, M. Shimoda] The effect of experimentally induced fever on the pharmacokinetics of cefepime administered intravenously at a dose of 75 mg/kg bw was studied in six healthy rabbits. The study was conducted in two consecutive phases, separated by a washout period of 2 weeks. Infection was induced by the intravenous inoculation of 5 × 108 cfu of Escherichia coli 24 h before the pharmacokinetic investigation was carried out. Serial blood samples for cefepime concentration determination were obtained for 48 h following drug administration. The concentrations of cefepime in the plasma were determined by a quantitative microbiological assay using an agar-gel diffusion method employing Bacillus subtilis ATCC 6633 as the test organism, with a level of detectability of approximately 0.10 μg/ml. Cefepime plasma concentrations versus time were evaluated by non-compartmental methods using WinNonLin. Cefepime was well tolerated and no serious adverse events were observed. Rectal temperature increased 1°C 24 h post injection in infected animals. Highly significant differences in the blood plasma concentrations of cefepime were observed between febrile and healthy animals at all the sampling times. This could explain the greater area under the plasma level-time curve of the drug in febrile compared with healthy animals. The results from pharmacokinetic calculations showed that both the distribution volume at steady state (V dss) and body clearance (CLtot) were affected in febrile as compared to healthy animals. The mean values of V dss and CLtot of cefepime in healthy rabbits were 1.168 L/kg and 0.303 L/kg/h, respectively. As compared with healthy animals, the mean estimates of V dss (0.917 L/kg) and CLtot (0.205 L/kg per h) of cefepime were significantly lower, whereas t 1/2λ, MRT and AUMC were significantly higher in febrile rabbits. It is concluded that, although experimental infection had an effect on the disposition kinetics of cefepime in healthy and febrile rabbits, this was not sufficiently pronounced to require alteration of the dosage during disease. Springer Science + Business Media, Inc., 2007 cefepime nationallicence pharmacokinetics nationallicence microbiological assay nationallicence healthy nationallicence febrile nationallicence rabbits nationallicence AUC : area under the curve from zero to infinity by the trapezoidal integral nationallicence AUMC : area under the moment curve nationallicence AGP : acid glycoprotein nationallicence bw : body weight nationallicence Cltot : total body clearance nationallicence cfu : colony-forming units nationallicence i.v. : intravenous(ly) nationallicence LPS : lipopolysaccharide nationallicence MRT : mean residence time nationallicence t 1/2λ : elimination half-life nationallicence V dss : volume of distribution at steady state nationallicence El-Aty A. Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt aut Goudah A. Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt aut Mouneir S. Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt aut Sunwoo Y. Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan aut Jang J. Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan aut Shin J. Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan aut Shim J. Division of Applied Bioscience and Biotechnology, College of Agriculture and Life Science, Chonnam National University, Gwangju, Korea aut Shimoda M. Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan aut Veterinary Research Communications Kluwer Academic Publishers 31/1(2007-01-01), 67-75 0165-7380 31:1<67 2007 31 11259 https://doi.org/10.1007/s11259-006-3405-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11259-006-3405-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- El-Aty A. Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt aut NATIONALLICENCE 700 1- Goudah A. Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt aut NATIONALLICENCE 700 1- Mouneir S. Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt aut NATIONALLICENCE 700 1- Sunwoo Y. Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan aut NATIONALLICENCE 700 1- Jang J. Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan aut NATIONALLICENCE 700 1- Shin J. Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Busan aut NATIONALLICENCE 700 1- Shim J. Division of Applied Bioscience and Biotechnology, College of Agriculture and Life Science, Chonnam National University, Gwangju, Korea aut NATIONALLICENCE 700 1- Shimoda M. Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan aut NATIONALLICENCE 773 0- Veterinary Research Communications Kluwer Academic Publishers 31/1(2007-01-01), 67-75 0165-7380 31:1<67 2007 31 11259 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer