| 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. |
