title: Toxicokinetics of cotyledoside following intravenous administration to sheep.
abstract: Cotyledoside, a bufadienolide cardiac glycoside, was administered intravenously to sheep in 2 studies. In experiment 1, sheep (n = 4) received 0.0135 mg/kg daily on 5 consecutive days and in the 2nd experiment, sheep (n = 4) received 0.027 mg/kg as a single dose. Jugular blood was collected at different time intervals and kinetic parameters were determined. The data fitted a 1-compartmental model. In both experiments a short half-life (t1/2) and mean residence time (MRT), a relative small volume of distribution (Vd(ss)) and rapid clearance were calculated. In the 1st experiment, t1/2 and MRT increased significantly (P < 0.007) from Day (D) 0 to D4. It is suggested that the rapid decline in plasma cotyledoside concentrations in sheep denotes rapid distribution of cotyledoside to the tissues or extracellular spaces and possible accumulation at the biophase.
authors.affiliation: Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa. cbotha@op.up.ac.za
authors.forename: C J
authors.initials: CJ
authors.lastname: Both
authors.forename: T
authors.initials: T
authors.lastname: Rundberget
authors.forename: G E
authors.initials: GE
authors.lastname: Swan
authors.forename: M S G
authors.initials: MS
authors.lastname: Mülders
authors.forename: A
authors.initials: A
authors.lastname: Flåøyen
mesh_terms: D000818:Animals; D002018:Bufanolides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002301:Cardiac Glycosides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D007275:Injections, Intravenous / Q000662:veterinary; D012756:Sheep / Q000097:blood / Q000378:metabolism*
chemical_list: D002018:Bufanolides; D002301:Cardiac Glycosides; C038322:cotyledoside