Effect of ketoprofen co-administration or febrile state on pharmacokinetic of cefepime in sheep/Ucinak ketoprofena ili vrucice na farmakokinetiku cefepima u ovaca

The pharmacokinetics of cefepime (20 mg/kg) were studied following intramuscular administration of cefepime alone, co-administered with ketoprofen (3 mg/kg) and in a febrile state (Escherichia coli LPS induced) in sheep. The concentration of cefepime in the serum was detected by High Performance Liquid Chromatography. Following single dose intravenous administration of cefepime, elimination half life (2.50 ± 0.05 h), the area under the curve (143.48 ± 7.36 µg.h/mL), body clearance (0.14 ± 0.01 L/h/kg) and volume of distribution (0.51 ± 0.03 L/kg) were determined. Following a single dose intramuscular administration of cefepime alone, peak serum concentration (28.76 ± 0.54 µg/mL) was obtained at 0.75 h. The absorption half life ([t.sub.1/2Kα]), volume of distribution ([Vd.sub.area]), total body clearance (C[1.sub.B]) and elimination half life ([t.sub.1/2β]) of cefepime were 0.16 ± 0.01 h, 1.02 ± 0.08 L/kg, 0.13 ± 0.01 L/h/kg and 5.31 ± 0.23 h, respectively. Following co-administration of ketoprofen (30.74 ± 1.22 µg/mL) and in a febrile condition, a higher peak serum concentration of cefepime (39.68 ± 1.13 µg/mL) was observed at 0.75 h and 1 h, respectively. However, no significant changes were reported in other pharmacokinetic parameters following co-administration of cefepime with ketoprofen. In a febrile state, absorption half life, area under the curve and bioavailability were significantly increased while the volume of distribution and clearance of cefepime were significantly decreased following intramuscular administration. Cefepime pharmacokinetic data (20 mg/kg) generated from the present study suggest that the drug may be administered with ketoprofen, and in febrile conditions in sheep, the drug may be given intramuscularly at 24 h intervals to combat susceptible bacterial infections. Key words: pharmacokinetic, cefepime, ketoprofen, fever, sheep Istrazena je farmakokinetika cefepima (20 mg/kg) nakon nj egove intramuskularne primj ene s ketoprofenom (3 mg/kg) u tijeku vrucice u ovaca izazvane lipopolisaharidima bakterije Escherichia coli. Koncentracija cefepima u serumu bila je odrecivana tekucinskom kromatografijom. Nakon jednokratne intravenske primjene poluzivot njegova izlucivanja iznosio je 2,50 ± 0,05 h, povrsina ispod koncentracijske krivulje bila je 143,48 ± 7,36 µg.h/mL, ukupni tjelesni klirens iznosio je 0,14 ± 0,01 L/h/kg, a volumen raspodjele 0,51 ± 0,03 L/kg. Nakon jednokratne intramuskularne primjene samo cefepima vrsna koncentracija u