Thalidomide pharmacokinetics in sheep |
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| Authors: | SL Smith P Singh D Harding D Lun JP Chambers |
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| Institution: | 1. Institute of Veterinary, Animal and Biological Sciences, Massey University, Tennent Drive, Palmerston North 4443, New Zealand;2. Institute of Fundamental Sciences, Massey University, Tennent Drive, Palmerston North 4474, New Zealand |
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| 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.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.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.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. |
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| Keywords: | Thalidomide sheep Johne's disease pharmacokinetics tumour necrosis factor alpha TNF-α |
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