The effect of induced fever on the biokinetics of norfloxacin and its interaction with probenecid in goats.
The kinetic profiles of norfloxacin were evaluated in afebrile, febrile and probenecid pre-treated (70 mg/kg orally) febrile goats after a single intravenous (i.v.) dose (5 mg/kg). Fever was induced and maintained for 12 h by injecting Escherichia coli endotoxin (0.2 microgram/kg, i.v.) and repeating it in half the dose (0.1 microgram/kg) 5 h later. The plasma pharmacokinetic values for norfloxacin were best represented using a two-compartment open model. The peak norfloxacin plasma level of 90.52 +/- 3.18 micrograms/ml attained in the probenecid pre-treated febrile goats was higher than that in the febrile (75.46 +/- 0.72 micrograms/ml) or afebrile goats (62.25 +/- 1.23 micrograms/ml). ClB and Kel values were significantly (p < 0.01) decreased in febrile compared with afebrile goats. These values were further reduced in febrile goats after probenecid pre-treatment. However, t1/2 beta was not affected by the fever-probenecid interaction. Norfloxacin may be used as an infusion with probenecid in caprine diseases where very high plasma levels are required to combat resistant organisms such as Bacteroides.
Jha
K
K
Department of Pharmacology and Toxicology, Ranchi Veterinary College, India.
Roy
B K
BK
Singh
R C
RC
D000704:Analysis of Variance; D000818:Animals; D004347:Drug Interactions; D004731:Endotoxins; D004926:Escherichia coli; D005260:Female; D005334:Fever / Q000503:physiopathology*; D006041:Goats; D008070:Lipopolysaccharides; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D009643:Norfloxacin / Q000097:blood / Q000493:pharmacokinetics*; D011339:Probenecid / Q000494:pharmacology*
D004731:Endotoxins; D008070:Lipopolysaccharides; D009643:Norfloxacin; D011339:Probenecid