Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate

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Abstract
Aliabadi, F. S., Lees, P. Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of marbofloxacin in calf serum, exudate and transudate.J. vet. Pharmacol. Therap.25,161–174.Marbofloxacin is a fluoroquinolone antimicrobial drug used in cattle for the treatment of respiratory infections. In this investigation the pharmacokinetics (PK) of marbofloxacin were determined after intravenous and intramuscular dosing at a dosage of 2 mg/kg. In addition theex vivopharmacodynamics (PD) of the drug were determined in serum and three types of tissue cage fluid (transudate, inflammatory exudate generated by carrageenan and exudate generated by lipopolysaccharide). Marbofloxacin PK was characterized by a high volume of distribution after dosing by both routes (1.28 L/kg intravenous and 1.25 L/kg intramuscular). Corresponding area under the concentration–time curve (AUC) and elimination half‐life (t½el) values were 9.99 and 10.11 μg h/mL and 4.23 and 4.33 h, respectively. Values ofAUCfor carrageenan‐induced exudate, lipopolysaccharide‐induced exudate and transudate were, respectively, 8.28, 7.83 and 7.75 μg h/mL after intravenous and 8.84, 8.53 and 8.52 μg h/mL after intramuscular dosing. Maximum concentration (Cmax) values were similar for the three tissue cage fluids after intravenous and intramuscular dosing. Forin vivoPK data values ofAUC:minimum inhibitory concentration (MIC) (AUIC) ratio for serum were 250 and 253, respectively, after intravenous and intramuscular dosing of marbofloxacin against a pathogenic strain ofMannheimia haemolytica(MIC=0.04 μg/mL). For all tissue cage fluidsAUICvalues were >194 and >213 after intravenous and intramuscular dosing, andCmax/MICratios were 9 or greater, indicating a likely high level of effectiveness in clinical infections caused byM. haemolyticaofMIC0.04 μg/mL or less. This was confirmed by bothin vitro(serum) andex vivo(serum, exudate and transudate) measurements, which demonstrated a concentration‐dependent killing profile for marbofloxacin againstM. haemolytica. Ex vivo, after 24‐h incubation, virtually all bacteria were killed (Emaxequation to theex vivoantibacterial data provided, for serum,AUIC24 hvalues of 37.1 for bacteriostasis, 46.3 for bactericidal activity and 119.6 for elimination of bacteria. These data may be used as a rational basis for setting dosing schedules which optimize clinical efficacy and minimize the opportunities for emergence of resistant organisms.

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