Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits

F. Sampieri, J. Alcorn, A. L. Allen, C. R. Clark, F. A. Vannucci, Nicola Pusterla, S. Mapes, K. R. Ball, P. M. Dowling, J. Thompson, L. R. Bernstein, C. J. Gebhart, D. L. Hamilton

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)486-499
Number of pages14
JournalJournal of Veterinary Pharmacology and Therapeutics
Volume37
Issue number5
DOIs
StatePublished - 2014

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Lawsonia Bacteria
gallium
Lawsonia intracellularis
Gallium
pharmacokinetics
Pharmacokinetics
Horses
rabbits
Rabbits
digestive system diseases
horses
mouth
Euthanasia
Serology
New Zealand
Half-Life
gallium maltolate
Spectrum Analysis
Iron
Immunohistochemistry

ASJC Scopus subject areas

  • veterinary(all)
  • Pharmacology

Cite this

Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits. / Sampieri, F.; Alcorn, J.; Allen, A. L.; Clark, C. R.; Vannucci, F. A.; Pusterla, Nicola; Mapes, S.; Ball, K. R.; Dowling, P. M.; Thompson, J.; Bernstein, L. R.; Gebhart, C. J.; Hamilton, D. L.

In: Journal of Veterinary Pharmacology and Therapeutics, Vol. 37, No. 5, 2014, p. 486-499.

Research output: Contribution to journalArticle

Sampieri, F, Alcorn, J, Allen, AL, Clark, CR, Vannucci, FA, Pusterla, N, Mapes, S, Ball, KR, Dowling, PM, Thompson, J, Bernstein, LR, Gebhart, CJ & Hamilton, DL 2014, 'Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits', Journal of Veterinary Pharmacology and Therapeutics, vol. 37, no. 5, pp. 486-499. https://doi.org/10.1111/jvp.12114
Sampieri, F. ; Alcorn, J. ; Allen, A. L. ; Clark, C. R. ; Vannucci, F. A. ; Pusterla, Nicola ; Mapes, S. ; Ball, K. R. ; Dowling, P. M. ; Thompson, J. ; Bernstein, L. R. ; Gebhart, C. J. ; Hamilton, D. L. / Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits. In: Journal of Veterinary Pharmacology and Therapeutics. 2014 ; Vol. 37, No. 5. pp. 486-499.
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title = "Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits",
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.",
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AU - Alcorn, J.

AU - Allen, A. L.

AU - Clark, C. R.

AU - Vannucci, F. A.

AU - Pusterla, Nicola

AU - Mapes, S.

AU - Ball, K. R.

AU - Dowling, P. M.

AU - Thompson, J.

AU - Bernstein, L. R.

AU - Gebhart, C. J.

AU - Hamilton, D. L.

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