M.V.Sc. dissertation
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Date
2005
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Publisher
AAU, Anand
Abstract
Cefepime, a fourth-generation semi-synthetic broad spectrum cephalosporin
has bactericidal action against broad range of bacteria including those that are
resistant to conventional antibacterial drugs. The present study was designed to
investigate pharmacokinetics of cefepime in Holstein-Friesian calves following single
dose intravenous and intramuscular administration at the dose rate of 5 mg kg-1 of
body weight. Drug concentration in serum was determined using High Performance
Liquid Chromatography (HPLC). Following intravenous and intramuscular
administration, the serum concentration-time curves were characteristic of a two
compartment open model.
Following intravenous administration the mean serum cefepime level of
44.93 5.47 g ml-1 was observed at 0.033 h (2 minutes). The therapeutically
effective concentration of cefepime ( 1.00 g ml-1) was maintained in serum up to
12 h. The distribution half-life (t1/2) and elimination half-life (t1/2) were 0.09 0.01
h and 3.70 0.16 h, respectively. The mean values of apparent volume of distribution
[Vd(area)] and volume of distribution of drug at steady-state (Vdss) were calculated to be
0.57 0.03 and 0.43 0.03 L kg-1, respectively. The mean value of total body
clearance (ClB) was 1.81 0.16 ml min-1 kg-1. The average values for area under
serum drug concentration-time curve (AUC) and area under first moment of curve
(AUMC) were 47.73 4.05 g h ml-1 and 190.3 19.9 g h2 ml-1. The average value
of mean residence time (MRT) was 3.95 0.11 h.
Following single dose intramuscular administration, the therapeutically
effective serum concentration was detectable at 0.083 h (5 minutes) and maintained
for 12 h. Peak serum concentration (8.61 0.36 g ml-1) was obtained at 1 h after
intramuscular administration. After rapid absorption of drug from the site of
administration (t1/2ka: 0.21 0.03 h), it was slowly eliminated from the body (t1/2: 6.71
0.42 h). The mean apparent volume of distribution [Vd(area)] and volume of
distribution of steady state (Vdss) were 0.99 0.08 and 0.81 0.05 L kg-1, respectively.
The mean value of total body clearance (ClB) was 1.72 0.08 ml min-1 kg-1.The mean
area under the serum concentration-time curve (AUC), mean area under first moment
of curve (AUMC) and mean residence time (MRT) were 47.45 1.13 g h ml-1,
363.88 23.6 g h2 ml-1 and 7.66 0.45 h, respectively. The bioavailability of
cefepime was 0.98 0.03 (98 3 per cent) following intramuscular administration.
The optimal dosage regimens for cefepime for intravenous and intramuscular
administration were computed. An appropriate intravenous dosage regimen of
cefepime in cow calves would be 4.20 mg kg-1 of body weight to be repeated every
12 h interval. It is suggested to administer drug intramuscularly at the dose rate of 5
mg kg-1 of body weight every 12 h for medication of cow calves. A more practical
approach would be to administer loading intravenous dose (4.20 mg kg-1) followed by
intramuscular dose (5.0 mg kg-1) repeated at every 12 h.
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Keywords
veterinary science, pharmacology, toxicology, study