Premium
Pharmacokinetics of gallium maltolate in L awsonia intracellularis ‐infected and uninfected rabbits
Author(s) -
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.
Publication year - 2014
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12114
Subject(s) - pharmacokinetics , lawsonia intracellularis , chemistry , cmax , bioavailability , medicine , gastroenterology , pharmacology , veterinary medicine
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.