title: Effects of endotoxin-induced fever and probenecid on disposition of enrofloxacin and its metabolite ciprofloxacin after intravascular administration of enrofloxacin in goats.
abstract: Pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in normal, febrile and probenecid-treated adult goats after single intravenous (i.v.) administration of enrofloxacin (5 mg/kg). Pharmacokinetic evaluation of the plasma concentration-time data of enrofloxacin and ciprofloxacin was performed using two- and one-compartment open models, respectively. Plasma enrofloxacin concentrations were significantly higher in febrile (0.75-7 h) and probenecid-treated (5-7 h) goats than in normal goats. The sum of enrofloxacin and ciprofloxacin concentrations in plasma > or =0.1 microg /mL was maintained up to 7 and 8 h in normal and febrile or probenecid-treated goats, respectively. The t1/2beta, AUC, MRT and ClB of enrofloxacin in normal animals were determined to be 1.14 h, 6.71 microg .h/mL, 1.5 h and 807 mL/h/kg, respectively. The fraction of enrofloxacin metabolized to ciprofloxacin was 28.8%. The Cmax., t1/2beta, AUC and MRT of ciprofloxacin in normal goats were 0.45 microg /mL, 1.79 h, 1.84 microg .h/mL and 3.34 h, respectively. As compared with normal goats, the values of t1/2beta (1.83 h), AUC (11.68 microg ? h/mL) and MRT (2.13 h) of enrofloxacin were significantly higher, whereas its ClB (430 mL/h/kg) and metabolite conversion to ciprofloxacin (8.5%) were lower in febrile goats. The Cmax. (0.18 microg /mL) and AUC (0.99 microg .h/mL) of ciprofloxacin were significantly decreased, whereas its t1/2beta (2.75 h) and MRT (4.58 h) were prolonged in febrile than in normal goats. Concomitant administration of probenecid (40 mg/kg, i.v.) with enrofloxacin did not significantly alter any of the pharmacokinetic variables of either enrofloxacin or ciprofloxacin in goats.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, IZATNAGAR-243 122 (U.P.), India. hct55@ivri.up.nic.in
authors.forename: G S
authors.initials: GS
authors.lastname: Rao
authors.forename: S
authors.initials: S
authors.lastname: Ramesh
authors.forename: A H
authors.initials: AH
authors.lastname: Ahmad
authors.forename: H C
authors.initials: HC
authors.lastname: Tripathi
authors.forename: L D
authors.initials: LD
authors.lastname: Sharma
authors.forename: J K
authors.initials: JK
authors.lastname: Malik
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D004731:Endotoxins / Q000633:toxicity*; D000077422:Enrofloxacin; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D024841:Fluoroquinolones; D006041:Goats; D006207:Half-Life; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D011339:Probenecid / Q000633:toxicity*; D015363:Quinolones / Q000097:blood / Q000493:pharmacokinetics*; D014528:Uricosuric Agents / Q000633:toxicity*
chemical_list: D000890:Anti-Infective Agents; D004731:Endotoxins; D024841:Fluoroquinolones; D015363:Quinolones; D014528:Uricosuric Agents; D000077422:Enrofloxacin; D002939:Ciprofloxacin; D011339:Probenecid