Pharmacokinetics of enrofloxacin HCl-2H2 O (ENRO-C), PK/PD, and Monte Carlo modeling vs. Leptospira spp. in cows.

The pharmacokinetics, PK/PD ratios, and Monte Carlo modeling of enrofloxacin HCl-2H2 O (Enro-C) and its reference preparation (Enro-R) were determined in cows. Fifty-four Jersey cows were randomly assigned to six groups receiving a single IM dose of 10, 15, or 20 mg/kg of Enro-C (Enro-C10 , Enro-C15 , Enro-C20 ) or Enro-R. Serial serum samples were collected and enrofloxacin concentrations quantified. A composite set of minimum inhibitory concentrations (MIC) of Leptospira spp. was utilized to calculate PK/PD ratios: maximum serum concentration/MIC (Cmax /MIC90 ) and area under the serum vs. time concentration of enrofloxacin/MIC (AUC0-24 /MIC90 ). Monte Carlo simulations targeted Cmax /MIC = 10 and AUC0-24 /MIC = 125. Mean Cmax obtained were 6.17 and 2.46 µg/ml; 8.75 and 3.54 µg/ml; and 13.89 and 4.25 µg/ml, respectively for Enro-C and Enro-R. Cmax /MIC90 ratios were 6.17 and 2.46, 8.75 and 3.54, and 13.89 and 4.25 for Enro-C and Enro-R, respectively. Monte Carlo simulations based on Cmax /MIC90  = 10 indicate that only Enro-C15 and Enro-C20 may be useful to treat leptospirosis in cows, predicting a success rate ≥95% when MIC50  = 0.5 µg/ml, and ≥80% when MIC90  = 1.0 µg/ml. Although Enro-C15 and Enro-C20 may be useful to treat leptospirosis in cattle, clinical trials are necessary to confirm this proposal.

Pharmacokinetics of enrofloxacin HCl-2H2O (Enro-C) in dogs and pharmacokinetic/pharmacodynamic Monte Carlo simulations against Leptospira spp.

Pharmacokinetic/pharmacodynamic (PK/PD) ratios of reference enrofloxacin (Enro-R) and enrofloxacin as HCl-2H2O (Enro-C), as well as Monte Carlo simulations based on composite MIC50 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-Roral and Enro-Coral, 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.