Back to Search
Start Over
Thalidomide pharmacokinetics in sheep.
- Source :
-
New Zealand veterinary journal [N Z Vet J] 2016 Jul; Vol. 64 (4), pp. 238-42. Date of Electronic Publication: 2016 Feb 05. - Publication Year :
- 2016
-
Abstract
- Aim: 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.<br />Method: 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.<br />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.<br />Conclusion: 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.
Details
- Language :
- English
- ISSN :
- 1176-0710
- Volume :
- 64
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- New Zealand veterinary journal
- Publication Type :
- Academic Journal
- Accession number :
- 26727254
- Full Text :
- https://doi.org/10.1080/00480169.2015.1130663