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J Vet Pharmacol Ther. 2019 May;42(3):300-308. doi: 10.1111/jvp.12748. Epub 2019 Feb 3.

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

Author information

1
Department of Physiology and Pharmacology, National Autonomous University of Mexico (UNAM), Mexico City, Mexico.
2
Department of Microbiology, National Autonomous University of Mexico (UNAM), Mexico City, Mexico.
3
Department of Statistics, Autonomous Technological Institute of Mexico (ITAM), Mexico City, Mexico.

Abstract

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.

KEYWORDS:

Enro-C; Leptospira spp.; PK/PD; cows; enrofloxacin; pharmacokinetics

PMID:
30714169
DOI:
10.1111/jvp.12748
[Indexed for MEDLINE]

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