Farmakokinetika cefepima u bivolske teladi s vrućicom izazvanom lipopolisaharidom bakterije E. coli

Abstract

The pharmacokinetics of cefepime after its single intravenous administration (10 mg/kg) was investigated in experimentally induced fever in buffalo calves (n = 4). The fever was induced by single/repeated intravenous injection of E. coli lipopolysaccaride (1 μg/kg). The drug was estimated in plasma samples by microbiological assay using E. coli (MTCC 739) test organism. The pharmacokinetic behaviour of cefepime in febrile animals was described by a two compartment open model. At 1 min, the concentration of cefepime in plasma was 40.8 ± 0.98 μg/mL which rapidly declined to 23.0 ± 0.64 μg/mL at 15 min. The drug was detected up to 24 h. The elimination half-life and volume of distribution were 3.00 ± 0.18 h and 0.42 ± 0.02 L/kg, respectively. The distribution half-life, AUC and total body clearance (ClB) were 0.08 ± 0.002 h, 101 ± 7.65 μg/mL.h and 98.8 ± 6.06 mL/kg/h, respectively. To maintain a minimum therapeutic concentration of 1 μg/mL, a satisfactory dosage regimen of cefepime in febrile buffalo calves would be 7 mg/kg repeated at 12 h intervals.Istražena je farmakokinetika cefepima u bivolske teladi (n = 4) s pokusno izazvanom vrućicom nakon njegove jednokratne intravenske primjene (10 mg/kg). Vrućica je bila izazvana jednokratnom ili ponovljenom intravenskom primjenom lipopolisaharida bakterije E. coli (1 μg/kg). Farmakokinetika lijeka određivana je u uzorcima plazme mikrobiološkim postupkom upotrebom soja E. coli (MTCC 739). Farmakokinetičko ponašanje cefepima u febrilnih životinja opisano je na osnovi dva otvorena modela. U prvoj minuti koncentracija cefepima u plazmi iznosila je 40,8 ± 0,98 μg/mL, a u 15. se naglo smanjila na 23,0 ± 0,64 μg/mL. Lijek je bio dokazan do 24 sata nakon davanja. Poluvrijeme njegova izlučivanja iznosilo je 3,00 ± 0,18 h, a količina raspodjele 0,42 ± 0,02 L/kg. Poluvrijeme njegove raspodjele iznosilo je 0,08 ± 0,002 h, površine ispod koncentracijske krivulje u plazmi 101 ± 7.65 μg/mL, a ukupni klirens iz organizma (ClB) 98,8 ± 6,06 mL/kg/h. Za održavanje minimalne terapijske koncentracije od 1 μg/mL cefepim bi u febrilne bivolske teladi trebalo davati u dozi od 7 mg/kg s ponovljenom primjenom u razmaku od 12 sati