Pulmonary disposition and pharmacokinetics of minocycline in the adult horse

Echeverria, Kate O

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https://hdl.handle.net/2142/97319 Copy

Description

Title

Pulmonary disposition and pharmacokinetics of minocycline in the adult horse

Author(s)

Echeverria, Kate O

Issue Date

2017-04-24

Director of Research (if dissertation) or Advisor (if thesis)

Lascola, Kara

Committee Member(s)

• Foreman, Jonathan
• Austin, Scott

Department of Study

Vet Clinical Medicine

Discipline

VMS-Veterinary Clinical Medcne

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• Pulmonary pharmacokinetics
• Equine
• Minocycline
• Horse pneumonia
• Pulmonary disposition
• Pulmonary epithelial lining fluid
• Bronchoalveolar lavage

Abstract

The purpose of this study was to determine the pharmacokinetics and pulmonary disposition of minocycline in horses after a single intravenous (IV) and intragastric (IG) dose and after multiple IG doses. The study hypotheses were that: minocycline would be present in the pulmonary epithelial lining fluid (PELF) and bronchoalveolar lavage (BAL) cells at concentrations exceeding those in plasma within 3 hours of IV or IG administration and achievable trough concentrations in the PELF and BAL cells after administration of IG minocycline would exceed a target concentration of 0.25 µg/mL. Seven healthy adult horses from the resident teaching herd were used for the two part study. For part one of the study, 6 horses received IV (2.2 mg/kg) or IG (4 mg/kg) minocycline in a randomized cross-over design. Plasma samples were collected prior to minocycline administration and 16 times within 36 hours. Bronchoalveolar lavages were performed 4 times within 24 hours for collection of PELF and BAL cells. For part two of the study, minocycline (4 mg/kg) was administered IG every 12 hours for 5 doses to 6 horses. Plasma samples were collected before minocycline administration and 20 times within 96 hours. Bronchoalveolar lavages were performed 6 times within 72 hours for collection of PELF samples and BAL cells. In study 1, mean bioavailability of minocycline was calculated at 48% (range 35- 75%). In study 2, at steady state, mean + SD maximum concentration (Cmax) of minocycline in the plasma was 2.3 + 1.3 µg/mL and the terminal half-life was 11.8 + 0.5 hours. The median (25th and 75th percentiles) time to peak concentration (Tmax) was 1.3 (1.0 – 1.5) hours. The Cmax and Tmax of minocycline in the PELF were 10.5 + 12.8 µg/mL and 9.0 (5.5 – 12.0) hours, respectively. The Cmax and Tmax for BAL cells were 0.24 + 0.1 µg/mL and 6.0 (0.0 – 6.0) hours, respectively. Oral bioavailability (48%) varied considerably among adult horses (35 – 75%). While minocycline was detected in the PELF and BAL cells within 3 hours of IV or IG drug administration, only concentrations in the PELF exceeded those in plasma. As predicted, PELF trough concentrations exceeded the target concentration of 0.25 µg/mL at all measured time points. Contrary to the study hypothesis, minocycline BAL cell concentrations at all measured time points were well below concentrations detected in plasma and PELF and the 0.25 µg/mL target concentration. It was concluded that minocycline distributes into the PELF and BAL cells of adult horses.

Graduation Semester

2017-05

Type of Resource

text

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http://hdl.handle.net/2142/97319

Copyright and License Information

Copyright 2017 Kate Echeverria

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