Enrofloxacin and marbofloxacin in horses: comparison of pharmacokinetic parameters, use of urinary and metabolite data to estimate first-pass effect and absorbed fraction

• Published in: Journal of veterinary pharmacology and therapeutics Vol. 29; no. 5; pp. 337 - 344
• Main Authors: PEYROU, M, BOUSQUET-MELOU, A, LAROUTE, V, VRINS, A, DOUCET, M.Y
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.10.2006; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: Administration, Oral; Animals; Anti-Infective Agents; Anti-Infective Agents - administration & dosage; Anti-Infective Agents - metabolism; Anti-Infective Agents - pharmacokinetics; antimicrobial agents; Area Under Curve; bioavailability; Biological Availability; blood chemistry; chemical composition; Ciprofloxacin; Ciprofloxacin - metabolism; Ciprofloxacin - pharmacokinetics; dosage; drug excretion; enrofloxacin; Enzyme Inhibitors; Enzyme Inhibitors - administration & dosage; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacokinetics; Female; Fluoroquinolones; Fluoroquinolones - administration & dosage; Fluoroquinolones - metabolism; Fluoroquinolones - pharmacokinetics; Half-Life; Horses; Injections, Intravenous; intravenous injection; Life Sciences; marbofloxacin; metabolites; oral administration; Pharmaceutical sciences; pharmacokinetics; Pharmacology; Quinolones; Quinolones - administration & dosage; Quinolones - metabolism; Quinolones - pharmacokinetics; uptake mechanisms; urine; Fluoroquinolones; Administration; Enzyme Inhibitors; Area Under Curve; Intravenous; Half-Life; Biological Availability; Oral; Anti-Infective Agents; Quinolones; Injections; Animals; Horses; Female; Ciprofloxacin
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1111/j.1365-2885.2006.00752.x

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 Vd₍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 AUC₀₋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.