Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (Rhinella marina)

Transdermal administration is an important method of pharmacologic drug therapy in amphibians, made possible by their unique skin physiology and permeability. Despite this, there are relatively few studies that investigate transdermal pharmacokinetics in amphibians. The objective of this study was t...

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Main Authors: Gregory Scott, Meghan M. Louis, Julie A. Balko, Claire M. Bublitz, Brigid V. Troan, Ronald E. Baynes, Dustin Smith, Larry J. Minter
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Veterinary Medicine International
Online Access:http://dx.doi.org/10.1155/2020/8863537
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author Gregory Scott
Meghan M. Louis
Julie A. Balko
Claire M. Bublitz
Brigid V. Troan
Ronald E. Baynes
Dustin Smith
Larry J. Minter
author_facet Gregory Scott
Meghan M. Louis
Julie A. Balko
Claire M. Bublitz
Brigid V. Troan
Ronald E. Baynes
Dustin Smith
Larry J. Minter
author_sort Gregory Scott
collection DOAJ
description Transdermal administration is an important method of pharmacologic drug therapy in amphibians, made possible by their unique skin physiology and permeability. Despite this, there are relatively few studies that investigate transdermal pharmacokinetics in amphibians. The objective of this study was to investigate the pharmacokinetics of transdermal flunixin meglumine applied topically to marine toads (Rhinella marina). Twenty-one adult marine toads were administered flunixin meglumine (3.3 mg/kg) topically on their dorsum and randomized (n = 7/group) to blood collection at two timepoints from the following: 1, 2, 4, 8, 12, and 24 hours (h), using a sparse sampling protocol. Plasma was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Samples were analyzed individually and reported as a mean of the samples at each timepoint. The mean peak plasma concentration was 6.31 µg/ml, area under the curve was 29.37 μg-h/mL, and elimination half-life was 2.79 h. No adverse effects were noted in any animals. A subset of 12 animals were euthanized at serial timepoints and necropsied. Histopathology of skin and major organs revealed one minimal superficial lesion in a single toad potentially attributable to flunixin meglumine administration; otherwise, no other treatment-related lesions were observed in 11 of 12 toads. A single topical dose of transdermal flunixin meglumine was rapidly absorbed in marine toads in the current study, and peak plasma concentrations exceeded therapeutic ranges established in cattle with no significant pathologic findings.
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spelling doaj-art-b9320efd5d054a6989daf61f9280e8662025-02-03T06:05:18ZengWileyVeterinary Medicine International2090-81132042-00482020-01-01202010.1155/2020/88635378863537Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (Rhinella marina)Gregory Scott0Meghan M. Louis1Julie A. Balko2Claire M. Bublitz3Brigid V. Troan4Ronald E. Baynes5Dustin Smith6Larry J. Minter7Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USADepartment of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USAEnvironmental Medicine Consortium, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USADepartment of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USAHanes Veterinary Medical Center, North Carolina Zoo, 4401 Zoo Parkway, Asheboro, NC 27205, USADepartment of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Drive, Raleigh, NC 27607, USAHanes Veterinary Medical Center, North Carolina Zoo, 4401 Zoo Parkway, Asheboro, NC 27205, USAHanes Veterinary Medical Center, North Carolina Zoo, 4401 Zoo Parkway, Asheboro, NC 27205, USATransdermal administration is an important method of pharmacologic drug therapy in amphibians, made possible by their unique skin physiology and permeability. Despite this, there are relatively few studies that investigate transdermal pharmacokinetics in amphibians. The objective of this study was to investigate the pharmacokinetics of transdermal flunixin meglumine applied topically to marine toads (Rhinella marina). Twenty-one adult marine toads were administered flunixin meglumine (3.3 mg/kg) topically on their dorsum and randomized (n = 7/group) to blood collection at two timepoints from the following: 1, 2, 4, 8, 12, and 24 hours (h), using a sparse sampling protocol. Plasma was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Samples were analyzed individually and reported as a mean of the samples at each timepoint. The mean peak plasma concentration was 6.31 µg/ml, area under the curve was 29.37 μg-h/mL, and elimination half-life was 2.79 h. No adverse effects were noted in any animals. A subset of 12 animals were euthanized at serial timepoints and necropsied. Histopathology of skin and major organs revealed one minimal superficial lesion in a single toad potentially attributable to flunixin meglumine administration; otherwise, no other treatment-related lesions were observed in 11 of 12 toads. A single topical dose of transdermal flunixin meglumine was rapidly absorbed in marine toads in the current study, and peak plasma concentrations exceeded therapeutic ranges established in cattle with no significant pathologic findings.http://dx.doi.org/10.1155/2020/8863537
spellingShingle Gregory Scott
Meghan M. Louis
Julie A. Balko
Claire M. Bublitz
Brigid V. Troan
Ronald E. Baynes
Dustin Smith
Larry J. Minter
Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (Rhinella marina)
Veterinary Medicine International
title Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (Rhinella marina)
title_full Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (Rhinella marina)
title_fullStr Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (Rhinella marina)
title_full_unstemmed Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (Rhinella marina)
title_short Pharmacokinetics of Transdermal Flunixin Meglumine Following a Single Dose in Marine Toads (Rhinella marina)
title_sort pharmacokinetics of transdermal flunixin meglumine following a single dose in marine toads rhinella marina
url http://dx.doi.org/10.1155/2020/8863537
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