Enrofloxacin and marbofloxacin in horses: comparison of pharmacokinetic parameters, use of urinary and metabolite data to estimate first-pass effect and absorbed fraction.
Enrofloxacin and marbofloxacin are two veterinary fluoroquinolones used to treat severe bacterial infections in horses. A repeated measures study has been designed to compare their pharmacokinetic parameters, to investigate their bioavailability and to estimate their absorbed fraction and first-pass effect by using plasma, urinary and metabolite data collected from five healthy mares. Clearance and V(d(ss)) were greater for enrofloxacin (mean +/- SD = 6.34 +/- 1.5 mL/min/kg and 2.32 +/- 0.32 L/kg, respectively) than for marbofloxacin (4.62 +/- 0.67 mL/min/kg and 1.6 +/- 0.25 L/kg, respectively). Variance of the AUC(0-inf) of marbofloxacin was lower than that for enrofloxacin, with, respectively, a CV = 15% and 26% intravenously and a CV = 31% and 55% after oral administration. Mean oral bioavailability was not significantly different between marbofloxacin (59%) and enrofloxacin (55%). The mean percentage of the dose eliminated unchanged in urine was significantly higher for marbofloxacin (39.7%) than that for enrofloxacin (3.4%). Absorbed fraction and first-pass effect were only determinable for enrofloxacin, whereas the percentage of the dose absorbed in the portal circulation was estimated to be 78% and the fraction not extracted during the first pass through the liver was 65%. Consequently, the moderate observed bioavailability of enrofloxacin appears to be mainly caused by hepatic first-pass effect.
Peyrou
M
M
Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada.
Bousquet-Melou
A
A
Laroute
V
V
Vrins
A
A
Doucet
M Y
MY
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002939:Ciprofloxacin / Q000378:metabolism / Q000493:pharmacokinetics; D000077422:Enrofloxacin; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D006207:Half-Life; D006736:Horses; D007275:Injections, Intravenous; D015363:Quinolones / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D015363:Quinolones; D000077422:Enrofloxacin; D002939:Ciprofloxacin; C080260:marbofloxacin