Pharmacokinetics of gallium maltolate in L awsonia intracellularis ‐infected and uninfected rabbits

Oral gallium maltolate ( G a M ) pharmacokinetics ( PK ) and intestinal tissue ( IT ) concentrations of elemental gallium ([ G a]) and iron ([ F e]) 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 G a M dose (50 mg/kg). Serial blood samples were collected from 0 to 216 h post‐treatment ( PT ) and IT samples after euthanasia. Serology, q PCR , 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); C max (0.50 ± 0.21 vs. 0.59 ± 0.42 μg/mL; P = 0.45); t max (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.