J Vet Sci.  2018 Sep;19(5):600-607. 10.4142/jvs.2018.19.5.600.

Pharmacokinetics of enrofloxacin HCl-2Hâ‚‚O (Enro-C) in dogs and pharmacokinetic/pharmacodynamic Monte Carlo simulations against Leptospira spp.

• Sumano H
• Ocampo L
• Tapia G
• Mendoza CD
• Gutierrez

• KMID: 2420928
• DOI: http://doi.org/10.4142/jvs.2018.19.5.600

Abstract

Pharmacokinetic/pharmacodynamic (PK/PD) ratios of reference enrofloxacin (Enro-R) and enrofloxacin as HCl-2Hâ‚‚O (Enro-C), as well as Monte Carlo simulations based on composite MICâ‚…â‚€ and MIC₉₀ (MIC, minimum inhibitory concentration) vs. Leptospira spp., were carried out in dogs after their intramuscular (IM) or oral administration (10 mg/kg). Plasma determination of enrofloxacin was achieved by means of high-performance liquid chromatography. Maximum plasma concentration values after oral administration were 1.47 ± 0.19 µg/mL and 5.3 ± 0.84 µg/mL for Enro-R and Enro-C, respectively, and 1.6 ± 0.12 µg/mL and 7.6 ± 0.93 µg/mL, respectively, after IM administration. Areas under the plasma vs. time concentration curve in 24 h (AUC₀₋₂₄) were 8.02 µg/mL/h and 36.2 µg/mL/h for Enro-R(oral) and Enro-C(oral), respectively, and 8.55 ± 0.85 µg/mL/h and 56.4 ± 6.21 µg/mL/h after IM administration of Enro-R and Enro-C, respectively. The PK/PD ratios and Monte Carlo simulations obtained with Enro-C, not Enro-R, indicated that its IM administration to dogs will result in therapeutic concentrations appropriate for treating leptospirosis. This is the first time enrofloxacin has been recommended to treat this disease in dogs.

Keyword

dogs; enrofloxacin; leptospirosis; pharmacodynamics; pharmacokinetics

MeSH Terms

Administration, Oral
Animals
Chromatography, Liquid
Dogs*
Leptospira*
Leptospirosis
Pharmacokinetics*
Plasma

Figure

• 

  Fig. 1 Comparative serum profiles of enrofloxacin in dogs (n = 8 for each group) after a single dose of either the reference preparation (Baytril 5% solution IM [Enro-RIM] or Baytril tablets [Enro-Roral]) or enrofloxacin HCl-2H2O (as a 5% injectable suspension [Enro-CIM] or as gelatin capsules [Enro-Coral]). In all groups, the dose administered was 10 mg/kg. IM, intramuscular.

• 

  Fig. 2 Probability of target attainment (CMAX/MIC50 = 10) after a single IM or oral dose (10 mg/kg) of a reference preparation of enrofloxacin (Baytril 5%; Enro-R) or enrofloxacin HCl 2H2O (Enro-C), based on a composite MIC50 derived from a small survey of in vitro susceptibilities of Leptospira spp. to enrofloxacin and from the available data in previous reports. CMAX, maximum serum concentration; MIC, minimum inhibitory concentration; IM, intramuscular.

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