title: Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in goats given enrofloxacin alone and in combination with probenecid.
abstract: The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were investigated in goats given enrofloxacin alone or in combination with probenecid. Enrofloxacin was administered i.m. at a dosage of 5 mg x kg(-1) alone or in conjunction with probenecid (40 mg x kg(-1), i.v.). Blood samples were drawn from the jugular vein at predetermined time intervals after drug injection. Plasma was separated and analysed simultaneously for enrofloxacin and ciprofloxacin by reverse-phase high performance liquid chromatography. The plasma concentration-time data for both enrofloxacin and ciprofloxacin were best described by a one-compartment open pharmacokinetic model. The elimination half-life (t(1/2beta)), area under the plasma concentration-time curve (AUC), volume of distribution (V(d(area))), mean residence time (MRT) and total systemic clearance (Cl(B)) were 1.39 h, 7.82 microg x h x mL, 1.52 L x kg(-1), 2.37 h and 802.9 mL x h(-1) x kg(-1), respectively. Enrofloxacin was metabolized to ciprofloxacin in goats and the ratio between the AUCs of ciprofloxacin and enrofloxacin was 0.34. The t(1/2beta), AUC and MRT of ciprofloxacin were 1.82 h, 2.55 microg x h x mL and 3.59 h, respectively. Following combined administration of probenecid and enrofloxacin in goats, the sum of concentrations of enrofloxacin and ciprofloxacin levels > or = 0.1 microg x mL(-1) persisted in plasma up to 12 h.Co-administration of probenecid did not affect the t(1/2beta), AUC, V(d (area)) and Cl(B) of enrofloxacin, whereas the values of t(1/2beta) (3.85 h), AUC (6.29 microg x h x mL), MRT (7.34 h) and metabolite ratio (0.86) of ciprofloxacin were significantly increased. The sum of both enrofloxacin and ciprofloxacin levels was > or = 0.1 microg x mL(-1) and was maintained in plasma up to 8 h in goats after i.m. administration of enrofloxacin alone. These data indicate that a 12 h dosing regime may be appropriate for use in goats.
authors.affiliation: Division of Pharmacology & Toxicology, Indian Veterinary Research Institute, Izatnagar, UP, 243 122, 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 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000077422:Enrofloxacin; D005260:Female; D024841:Fluoroquinolones; D006041:Goats / Q000378:metabolism*; D006207:Half-Life; D007273:Injections, Intramuscular / Q000662:veterinary; D011339:Probenecid / Q000008:administration & dosage; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014528:Uricosuric Agents / Q000008:administration & dosage
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D024841:Fluoroquinolones; D015363:Quinolones; D014528:Uricosuric Agents; D000077422:Enrofloxacin; D002939:Ciprofloxacin; D011339:Probenecid