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

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

doi:10.1111/jvp.12114

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

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

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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); 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.

Original language	English (US)
Pages (from-to)	486-499
Number of pages	14
Journal	Journal of Veterinary Pharmacology and Therapeutics
Volume	37
Issue number	5
DOIs	https://doi.org/10.1111/jvp.12114
State	Published - 2014

Bibliographical note

Funding Information:
Our sincerest thanks are extended to R.T. Orchard, DVM; K.M.N. MacLellan, DVM; K.C. Smith, DO; and Ms. A.J. Anto-nopoulos, BSc, for their help during sample collection; to the ACU personnel at the Western College of Veterinary Medicine, University of Saskatchewan, for their expert technical support; and to Ms. A. Gebhart for her help with editing the manuscript. This study was funded by a 2009 Equine Health Research Fund Grant at the Western College of Veterinary Medicine, University of Saskatchewan. Drs. Sampieri and Ball were fellows of the CIHR-THRUST (Canadian Institutes of Health Research – Training Grant in Health Research Using Synchrotron Techniques) Grant. Dr. Vannucci was supported by the Brazilian Government sponsoring agency ‘Conselho Nacional de Desenvolvimento Cientifico e Tecnologico’ (CNPq).

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© 2014 John Wiley & Sons Ltd

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10.1111/jvp.12114

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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. (2014). Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits. Journal of Veterinary Pharmacology and Therapeutics, 37(5), 486-499. https://doi.org/10.1111/jvp.12114

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

@article{9a1907669ca94418be423975fdc70e1c,

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{\textendash}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.",

author = "F. Sampieri and J. Alcorn and Allen, \{A. L.\} and Clark, \{C. R.\} and Vannucci, \{F. A.\} and N. Pusterla and S. Mapes and Ball, \{K. R.\} and Dowling, \{P. M.\} and J. Thompson and Bernstein, \{L. R.\} and Gebhart, \{C. J.\} and Hamilton, \{D. L.\}",

note = "Funding Information: Our sincerest thanks are extended to R.T. Orchard, DVM; K.M.N. MacLellan, DVM; K.C. Smith, DO; and Ms. A.J. Anto-nopoulos, BSc, for their help during sample collection; to the ACU personnel at the Western College of Veterinary Medicine, University of Saskatchewan, for their expert technical support; and to Ms. A. Gebhart for her help with editing the manuscript. This study was funded by a 2009 Equine Health Research Fund Grant at the Western College of Veterinary Medicine, University of Saskatchewan. Drs. Sampieri and Ball were fellows of the CIHR-THRUST (Canadian Institutes of Health Research {\textendash} Training Grant in Health Research Using Synchrotron Techniques) Grant. Dr. Vannucci was supported by the Brazilian Government sponsoring agency {\textquoteleft}Conselho Nacional de Desenvolvimento Cientifico e Tecnologico{\textquoteright} (CNPq). Publisher Copyright: {\textcopyright} 2014 John Wiley \& Sons Ltd",

year = "2014",

doi = "10.1111/jvp.12114",

language = "English (US)",

volume = "37",

pages = "486--499",

journal = "Journal of Veterinary Pharmacology and Therapeutics",

issn = "0140-7783",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "5",

}

TY - JOUR

T1 - Pharmacokinetics of gallium maltolate in Lawsonia intracellularis-infected and uninfected rabbits

AU - Sampieri, F.

AU - Alcorn, J.

AU - Allen, A. L.

AU - Clark, C. R.

AU - Vannucci, F. A.

AU - Pusterla, N.

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.

N1 - Funding Information: Our sincerest thanks are extended to R.T. Orchard, DVM; K.M.N. MacLellan, DVM; K.C. Smith, DO; and Ms. A.J. Anto-nopoulos, BSc, for their help during sample collection; to the ACU personnel at the Western College of Veterinary Medicine, University of Saskatchewan, for their expert technical support; and to Ms. A. Gebhart for her help with editing the manuscript. This study was funded by a 2009 Equine Health Research Fund Grant at the Western College of Veterinary Medicine, University of Saskatchewan. Drs. Sampieri and Ball were fellows of the CIHR-THRUST (Canadian Institutes of Health Research – Training Grant in Health Research Using Synchrotron Techniques) Grant. Dr. Vannucci was supported by the Brazilian Government sponsoring agency ‘Conselho Nacional de Desenvolvimento Cientifico e Tecnologico’ (CNPq). Publisher Copyright: © 2014 John Wiley & Sons Ltd

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85006375120

UR - https://www.scopus.com/pages/publications/85006375120#tab=citedBy

U2 - 10.1111/jvp.12114

DO - 10.1111/jvp.12114

M3 - Article

AN - SCOPUS:85006375120

SN - 0140-7783

VL - 37

SP - 486

EP - 499

JO - Journal of Veterinary Pharmacology and Therapeutics

JF - Journal of Veterinary Pharmacology and Therapeutics

IS - 5

ER -

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

Abstract

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