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Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non-anesthetized Recordings
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Thalidomide pharmacokinetics in sheep.

S L Smith1, P Singh1, D Harding2

  • 1a Institute of Veterinary, Animal and Biological Sciences , Massey University , Tennent Drive, Palmerston North 4443 , New Zealand.

New Zealand Veterinary Journal
|January 5, 2016
PubMed
Summary
This summary is machine-generated.

Oral thalidomide in sheep demonstrated good bioavailability (89%) with pharmacokinetic parameters similar to humans. Topical application did not yield detectable plasma concentrations, suggesting limited efficacy for this route.

Keywords:
Johne's diseaseTNF-αThalidomidepharmacokineticssheeptumour necrosis factor alpha

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Area of Science:

  • Veterinary Pharmacology
  • Pharmacokinetics
  • Drug Development

Background:

  • Thalidomide has immunomodulatory properties relevant to chronic inflammatory diseases.
  • Understanding thalidomide pharmacokinetics in sheep is crucial for its potential use as a disease model.

Purpose of the Study:

  • To determine the pharmacokinetic parameters of thalidomide in sheep after intravenous, oral, and topical administration.
  • To compare sheep thalidomide pharmacokinetics with human data.

Main Methods:

  • Sheep lambs received single doses of thalidomide via intravenous, oral, or topical routes, with plasma concentrations analyzed using HPLC.
  • Pharmacokinetic parameters including half-life (T1/2), time to maximum concentration (Tmax), and maximum concentration (Cmax) were calculated.

Main Results:

  • Oral thalidomide showed 89% bioavailability with a T1/2 of 7.2 hours, Tmax of 3.0 hours, and Cmax of 1,767.3 ng/mL.
  • Intravenous administration yielded a T1/2 of 5.0 hours, while topical application in DMSO did not result in detectable plasma levels.

Conclusions:

  • Topical thalidomide in DMSO is not an effective route for achieving systemic exposure in sheep.
  • Oral thalidomide pharmacokinetics in sheep resemble human profiles, supporting its use as a model for inflammatory conditions like Johne's disease.