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.
Department of Pharmacology and Toxicology, Ranchi Veterinary College, India.
K
K
Jha
B K
BK
Roy
R C
RC
Singh
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