Pharmacokinetics of ibafloxacin following intravenous and oral administration to healthy Beagle dogs.
The pharmacokinetics of ibafloxacin, a new veterinary fluoroquinolone antimicrobial agent, was studied following intravenous (i.v.) and oral administration to healthy dogs. The mean absolute bioavailability of ibafloxacin after oral doses of 7.5, 15 and 30 mg/kg ranged from 69 to 81%, indicating that ibafloxacin was well absorbed by dogs. Ibafloxacin was also absorbed rapidly [time of maximum concentration (t(max)) 1.5 h], reaching a mean maximum concentration (C(max)) of 6 microg/mL at 15 mg/kg, well distributed in the body [large volume of distribution at steady state (V(ss)) and V(area) of 1.1 L/kg and 4 L/kg, respectively], and exhibited an elimination half-life of 5.2 h and a low total body clearance (8.7 mL/min/kg). Both C(max) and area under the concentration-time curve (AUC) showed dose proportionality over the dose range tested (7.5-30 mg/kg). The pharmacokinetics of ibafloxacin was similar following single and repeated dosage regimens, implying no significant accumulation in plasma. Food promoted the absorption of ibafloxacin by increasing C(max) and AUC, but did not change t(max). High amounts of the metabolites, mainly 8-hydroxy- and, 7-hydroxy-ibafloxacin were excreted in urine and faeces, either unchanged or as glucuronide conjugates. Following oral administration of 15 mg ibafloxacin/kg, the total recovery of ibafloxacin, its metabolites and conjugates in urine and faeces was 61.9-99.9% of the dose within 48 h.
Coulet
M
M
Intervet Pharma R & D S.A., Angers Technopole, Rue Olivier de Serres, BP 67131, 49071 Beaucouzé Cedex, France. mcoulet@intervet.com
Van Borssum Waalkes
M
M
Leeuwenkamp
O R
OR
Cox
P
P
Lohuis
J
J
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004285:Dogs / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones; D007262:Infusions, Intravenous / Q000662:veterinary; D008297:Male; D011807:Quinolizines / Q000494:pharmacology*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D011807:Quinolizines; C049886:ibafloxacin