Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits

F. Sampieri, J. Alcorn, A. L. Allen, C. R. Clark, F. A. Vannucci, N. Pusterla, S. Mapes, K. R. Ball, P. M. Dowling, J. Thompson, L. R. Bernstein, C. J. Gebhart, D. L. Hamilton

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Abstract

Oral gallium maltolate (GaM) pharmacokinetics (PK) and intestinal tissue (IT) concentrations of elemental gallium ([Ga]) and iron ([Fe]) were investigated in a rabbit model of equine proliferative enteropathy (EPE). New Zealand white does (uninfected controls and EPE-infected, n = 6/group) were given a single oral GaM dose (50 mg/kg). Serial blood samples were collected from 0 to 216 h post-treatment (PT) and IT samples after euthanasia. Serology, qPCR, and immunohistochemistry confirmed, or excluded, EPE. Blood and IT [Ga] and [Fe] were determined using inductively coupled plasma–mass spectrometry. PK parameters were estimated through noncompartmental approaches. For all statistical comparisons on [Ga] and [Fe] α = 5%. The Ga log-linear terminal phase rate constant was lower in EPE rabbits vs. uninfected controls [0.0116 ± 0.004 (SD) vs. 0.0171 ± 0.0028 per hour; P = 0.03]; but half-life (59.4 ± 24.0 vs. 39.4 ± 10.8 h; P = 0.12); Cmax (0.50 ± 0.21 vs. 0.59 ± 0.42 μg/mL; P = 0.45); tmax (1.75 ± 0.41 vs. 0.9 ± 0.37 h; P = 0.20); and oral clearance (6.743 ± 1.887 vs. 7.208 ± 2.565 L/h; P = 0.74) were not. IT's [Ga] and [Fe] were higher (P < 0.0001) in controls. In conclusion, although infection reduces IT [Ga] and [Fe], a 48 h GaM dosing interval is appropriate for multidose studies in EPE rabbits.

Original languageEnglish (US)
Pages (from-to)486-499
Number of pages14
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume37
Issue number5
DOIs
StatePublished - 2014

Bibliographical note

Funding Information:
Our sincerest thanks are extended to R.T. Orchard, DVM; K.M.N. MacLellan, DVM; K.C. Smith, DO; and Ms. A.J. Anto-nopoulos, BSc, for their help during sample collection; to the ACU personnel at the Western College of Veterinary Medicine, University of Saskatchewan, for their expert technical support; and to Ms. A. Gebhart for her help with editing the manuscript. This study was funded by a 2009 Equine Health Research Fund Grant at the Western College of Veterinary Medicine, University of Saskatchewan. Drs. Sampieri and Ball were fellows of the CIHR-THRUST (Canadian Institutes of Health Research – Training Grant in Health Research Using Synchrotron Techniques) Grant. Dr. Vannucci was supported by the Brazilian Government sponsoring agency ‘Conselho Nacional de Desenvolvimento Cientifico e Tecnologico’ (CNPq).

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