title: Pharmacokinetics of ammonium tetrathiomolybdate following intravenous administration in sheep.
abstract: South African Mutton Merino wethers (n = 5) were each dosed with 2.5 g copper oxide needles. Three weeks later the sheep were placed on stainless steel metabolic crates to facilitate urine and faecal collection. Ammonium tetrathiomolybdate (TTM) (1.7 mg kg-1) was administered intravenously, blood samples were collected at intervals and different pharmacokinetic parameters for TTM were determined and are presented. Serum molybdenum concentration data were best described by a 2-compartmental open model with first order rate constants. An elimination half-life (T1/2 beta) of 396.8 min, steady state volume of distribution (Vdss) of 0.8 e kg-1 and total body clearance (C1B) of 1.53 ml kg-1 min-1 were observed using non-linear compartmental analysis. A significant (p < or = 0.05) increase in molybdenum excretion in the faeces occurred at 24 and 48 h following TTM administration. No increase in faecal and urinary copper excretion could be demonstrated, probably because the sheep were not copper-loaded. However, before a shorter dosage interval can be recommended for the treatment of sheep during the haemolytic crisis of chronic copper poisoning, further research in copper-loaded sheep is indicated.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Republic of South Africa.
authors.forename: C J
authors.initials: CJ
authors.lastname: Botha
authors.forename: G E
authors.initials: GE
authors.lastname: Swan
authors.forename: P P
authors.initials: PP
authors.lastname: Minnaar
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003300:Copper / Q000097:blood / Q000506:poisoning; D008297:Male; D008982:Molybdenum / Q000493:pharmacokinetics*; D012756:Sheep / Q000097:blood*; D012757:Sheep Diseases / Q000097:blood / Q000517:prevention & control
chemical_list: D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate