title: Thalidomide pharmacokinetics in sheep.
abstract: OBJECTIVE
  To determine the half life (T1/2), time taken to reach maximum plasma concentration (Tmax) and maximum plasma concentration (Cmax) of thalidomide in sheep following I/V, oral and topical treatment with a single dose of thalidomide.
  
  
  METHODS
  Three groups of 4-6-month-old ram lambs were treated with thalidomide dissolved in dimethylsulphoxide (DMSO). The first group (n=10) was treated I/V with 100 mg thalidomide in 2 mL DMSO; the second group (n=8) received 400 mg thalidomide in 2 mL DMSO orally, and the third group (n=8) had 400 mg thalidomide in 4 mL DMSO applied topically. Plasma samples were collected up to 36 hours after treatment, snap-frozen at -80°C and analysed for concentrations of thalidomide using high performance liquid chromatography.
  
  
  RESULTS
  Following I/V administration, T1/2 was 5.0 (SEM 0.4) hours, volume of distribution was 3,372.0 (SEM 244.3) mL/kg and clearance was 487.1 (SEM 46.1) mL/hour.kg. Topical application of 400 mg thalidomide did not increase plasma concentrations. Following oral administration, thalidomide bioavailability was 89%, with T1/2, Tmax, and Cmax being 7.2 (SEM 0.8) hours, 3.0 (SEM 0.4) hours and 1,767.3 (SEM 178.1) ng/mL, respectively.
  
  
  CONCLUSIONS
  Topical administration using DMSO as a solvent did not increase concentrations of thalidomide in plasma. The mean pharmacokinetic parameters determined following oral treatment with 400 mg of thalidomide were similar to those reported in humans receiving a single 400 mg oral dose (T1/2 7.3 hours; Tmax 4.3 hours and Cmax 2,820 ng/mL). There is potential for thalidomide to be used as a model for the treatment of chronic inflammatory conditions in sheep, such as Johne's disease, where tumour necrosis factor alpha plays a pathogenic role.
authors.affiliation: a Institute of Veterinary, Animal and Biological Sciences , Massey University , Tennent Drive, Palmerston North 4443 , New Zealand.
authors.forename: S L
authors.initials: SL
authors.lastname: Smith
authors.affiliation: a Institute of Veterinary, Animal and Biological Sciences , Massey University , Tennent Drive, Palmerston North 4443 , New Zealand.
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.affiliation: b Institute of Fundamental Sciences , Massey University , Tennent Drive, Palmerston North 4474 , New Zealand.
authors.forename: D
authors.initials: D
authors.lastname: Harding
authors.affiliation: b Institute of Fundamental Sciences , Massey University , Tennent Drive, Palmerston North 4474 , New Zealand.
authors.forename: D
authors.initials: D
authors.lastname: Lun
authors.affiliation: a Institute of Veterinary, Animal and Biological Sciences , Massey University , Tennent Drive, Palmerston North 4443 , New Zealand.
authors.forename: J P
authors.initials: JP
authors.lastname: Chambers
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D001682:Biological Availability; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D012756:Sheep / Q000097:blood*; D013792:Thalidomide / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D013792:Thalidomide
keywords: Johne's disease; TNF-α; Thalidomide; pharmacokinetics; sheep; tumour necrosis factor alpha