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 language||English (US)|
|Number of pages||14|
|Journal||Journal of Veterinary Pharmacology and Therapeutics|
|State||Published - 2014|
Bibliographical noteFunding 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).
© 2014 John Wiley & Sons Ltd