Pharmacokinetics, milk penetration and PK/PD analysis by Monte Carlo simulation of marbofloxacin, after intravenous and intramuscular administration to lactating goats

LORENZUTTI AUGUSTO MATÍAS; LITTERIO NICOLÁS JAVIER; HIMELFARB MARTÍN ALEJANDRO; ZARAZAGA MARÍA DEL PILAR; SAN ANDRÉS MANUEL IGNACIO; DE LUCAS BURNEO JOSÉ JULIO

JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS

WILEY-BLACKWELL PUBLISHING, INC

Año: 2017 vol. 40 p. 629 - 640

0140-7783

The main objectives of this study were: (1) to evaluate the serum pharmacokinetic behavior and milk penetration of marbofloxacin (5 mg/kg), after intravenous (IV) and intramuscular (IM) administration in lactating goats and simulate a multi-dose regimen on steady-state conditions, (2) to determine the MIC and MPC of coagulase negative staphylococci (CNS) isolated from caprine mastitis in Córdoba, Argentina, and (3) to make a PK/PD analysis by Monte Carlo simulation from steady-state pharmacokinetic parameters of marbofloxacin (MFX) by IV and IM routes to evaluate the efficacy and risk of the emergence of resistance. The study was carried out with six healthy, female, adult Anglo Nubian lactating goats. Marbofloxacin was administered at 5 mg/kg bw by IV and IM route. Serum and milk concentrations of marbofloxacin were determined with HPLC/uv. From 106 regional strains of CNS isolated from caprine mastitis in herds from Córdoba, Argentina, MICs and MPCs were obtained. MIC90 and MPC90 were 0.4 and 6.4 µg/mL, respectively. MIC and MPC-based PK/PD analysis by Monte Carlo simulation indicates that IV and IM administration of MFX in lactating goats may not be adequate to recommend it as an empirical therapy against CNS, because the most exigent endpoints were not reached. Moreover, this dose regimen could increase the probability of selecting mutants and resulting in emergence of resistance. Based on the results of Monte Carlo simulation, the optimal dose of MFX to achieve an adequate antimicrobial efficacy should be 10 mg/kg, but it is important take into account that fluoroquinolones are substrates of efflux pumps, and this fact may determine that assumption of linear pharmacokinetics at high doses of MFX may be incorrect.