Pharmacokinetics of marbofloxacin in mature horses after single intravenous and intramuscular administration.
The pharmacokinetic behaviour of marbofloxacin, a new fluoroquinolone antimicrobial agent developed exclusively for veterinary use, was studied in mature horses (n = 5) after single-dose i.v. and i.m. administrations of 2 mg/kg bwt. Drug concentrations in plasma were determined by high performance liquid chromatography (HPLC) and data obtained were subjected to compartmental and noncompartmental kinetic analysis. This compound presents a relatively high volume of distribution (V(SS) = 1.17 +/- 0.18 l/kg), which suggests good tissue penetration, and a total body clearance (Cl) of 0.19 +/- 0.042 l/kgh, which is related to a long elimination half-life (t(1/2beta) = 4.74 +/- 0.8 h and 5.47 +/- 1.33 h i.v. and i.m. respectively). Marbofloxacin was rapidly absorbed after i.m. administration (MAT = 33.8 +/- 14.2 min) and presented high bioavailability (F = 87.9 +/- 6.0%). Pharmacokinetic parameters are not significantly different between both routes of administration (P>0.05). After marbofloxacin i.m. administration, no adverse reactions at the site of injection were observed. Serum CK activity levels 12 h after administration increased over 8-fold (range 3-15) compared with pre-injection levels, but this activity decreased to 3-fold during the 24 h follow-up period. Based on the value of surrogate markers to predict clinical success, Cmax/MIC ratio or AUC/MIC ratio, single daily marbofloxacin dose of 2 mg/kg bwt may not be effective in treating infections in horses caused by pathogens with an MIC > or = 0.25 microg/ml. However, if we use a classical antimicrobial efficacy criteria, marbofloxacin can reach a high plasma peak concentration and maintain concentrations higher than MICs determined for marbofloxacin against most gram-negative veterinary pathogens throughout the administration period. Taking into account the fact that fluoroquinolones are considered to have a concentration-dependent effect and a long postantibiotic effect against gram-negative bacteria, a dose of 2 mg/kg bwt every 24 h could be adequate for marbofloxacin in horses.
Facultad de Veterinaria, Universidad Complutense de Madrid, Spain.
M
M
Carretero
C
C
Rodríguez
M I
MI
San Andrés
P
P
Forés
J J
JJ
de Lucas
J
J
Nieto
S
S
Waxman
M D
MD
San Andrés
F
F
González
D000042:Absorption; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D001424:Bacterial Infections / Q000188:drug therapy / Q000662:veterinary; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D015169:Colony Count, Microbial / Q000662:veterinary; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones; D006734:Horse Diseases / Q000188:drug therapy / Q000382:microbiology; D006736:Horses / Q000097:blood / Q000378:metabolism*; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D008657:Metabolic Clearance Rate; D015363:Quinolones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D014018:Tissue Distribution; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; C080260:marbofloxacin