title: Pharmacologic evaluation of ammonium tetrathiomolybdate after intravenous and oral administration to healthy dogs.
abstract: OBJECTIVE
  To evaluate pharmacokinetics of ammonium tetrathiomolybdate (TTM) after IV and oral administration to dogs and effects of TTM administration on trace mineral concentrations.
  
  
  METHODS
  8 adult Beagles and Beagle crossbreds (4 sexually intact males and 4 sexually intact females).
  
  
  METHODS
  Dogs received TTM (1 mg/kg) IV and orally in a randomized crossover study. Serum molybdenum and copper concentrations were measured via inductively coupled plasma mass spectrometry in samples obtained 0 to 72 hours after administration. Pharmacokinetics was determined via noncompartmental analysis.
  
  
  RESULTS
  For IV administration, mean ± SD terminal elimination rate constant, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours(-1), 4.9 ± 0.6 μg/mL, 30.7 ± 5.4 μg/mL•h, and 27.7 ± 6.8 hours, respectively. For oral administration, mean ± SD terminal elimination rate constant, time to maximum concentration, maximum concentration, area under the curve, and half-life were 0.03 ± 0.01 hours(-1), 3.0 ± 3.5 hours, 0.2 ± 0.4 μg/mL, 6.5 ± 8.0 μg/mL•h, and 26.8 ± 8.0 hours, respectively. Oral bioavailability was 21 ± 22%. Serum copper concentrations increased significantly after IV and oral administration. Emesis occurred after IV (2 dogs) and oral administration (3 dogs).
  
  
  CONCLUSIONS
  Pharmacokinetics for TTM after a single IV and oral administration was determined for clinically normal dogs. Absorption of TTM after oral administration was variable. Increased serum copper concentrations suggested that TTM mobilized tissue copper. Further studies will be needed to evaluate the potential therapeutic use of TTM in copper-associated chronic hepatitis of dogs.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Chan
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Langlois
authors.forename: John P
authors.initials: JP
authors.lastname: Buchweitz
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Lehner
authors.forename: N Bari
authors.initials: NB
authors.lastname: Olivier
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Herdt
authors.forename: Marc B
authors.initials: MB
authors.lastname: Bailie
authors.forename: William D
authors.initials: WD
authors.lastname: Schall
mesh_terms: D061605:Administration, Intravenous / Q000662:veterinary; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002614:Chelating Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D008297:Male; D008982:Molybdenum / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014131:Trace Elements / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D014131:Trace Elements; D008982:Molybdenum; C020809:tetrathiomolybdate