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.
authors.affiliation: Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Sampieri
authors.forename: J
authors.initials: J
authors.lastname: Alcorn
authors.forename: A L
authors.initials: AL
authors.lastname: Allen
authors.forename: C R
authors.initials: CR
authors.lastname: Clark
authors.forename: F A
authors.initials: FA
authors.lastname: Vannucci
authors.forename: N
authors.initials: N
authors.lastname: Pusterla
authors.forename: S
authors.initials: S
authors.lastname: Mapes
authors.forename: K R
authors.initials: KR
authors.lastname: Ball
authors.forename: P M
authors.initials: PM
authors.lastname: Dowling
authors.forename: J
authors.initials: J
authors.lastname: Thompson
authors.forename: L R
authors.initials: LR
authors.lastname: Bernstein
authors.forename: C J
authors.initials: CJ
authors.lastname: Gebhart
authors.forename: D L
authors.initials: DL
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D045824:Desulfovibrionaceae Infections / Q000188:drug therapy / Q000382:microbiology*; D005260:Female; D006207:Half-Life; D020639:Lawsonia Bacteria; D009942:Organometallic Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011753:Pyrones / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D011817:Rabbits
chemical_list: D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; D011753:Pyrones; C512662:gallium maltolate