Pharmacokinetics of gallium maltolate in Lawsonia intracellularis‐infected and uninfected rabbits. Issue 5 (15th March 2014)

• Record Type: Journal Article
• Authors: Sampieri, F.; Alcorn, J.; Allen, A. L.; Clark, C. R.; Vannucci, F. A.; Pusterla, N.; Mapes, S.; Ball, K. R.; Dowling, P. M.; Thompson, J.; Bernstein, L. R.; Gebhart, C. J.; Hamilton, D. L.
• Is Part Of: Journal of veterinary pharmacology and therapeutics. Volume 37:Issue 5(2014)
• Page Start: 486
• Page End: 499
• Publication Date: 2014-03-15
• Subjects: Veterinary pharmacology -- Periodicals; Therapeutics -- Periodicals; 636.0895105
• DOI: 10.1111/jvp.12114
• Languages: English
• ISSNs: 0140-7783

Abstract

<abstract abstract-type="main" id="jvp12114-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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, <italic>n</italic> = 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] <italic>α</italic> = 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; <italic>P </italic>=<italic> </italic>0.03]; but half‐life (59.4 ± 24.0 vs. 39.4 ± 10.8 h; <italic>P </italic>=<italic> </italic>0.12); <italic>C</italic><sub>max</sub> (0.50 ± 0.21 vs. 0.59 ± 0.42 μg/mL; <italic>P </italic>=<italic> </italic>0.45); <italic>t</italic><sub>max</sub> (1.75 ± 0.41 vs. 0.9 ± 0.37 h; <italic>P </italic>=<italic> </italic>0.20); and oral clearance (6.743 ± 1.887 vs. 7.208 ± 2.565 L/h; <italic>P </italic>=<italic> </italic>0.74) were not. IT's [Ga] and [Fe] were higher (<italic>P </italic><<italic> </italic>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.</p> </abstract>