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Subcutaneously implanted tissue chambers--a pharmacokinetic study.

C R Clarke1, C R Short, D W Bourne

  • 1Department of Veterinary Physiology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803.

Journal of Veterinary Pharmacology and Therapeutics
|September 1, 1989
PubMed
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This study characterized drug distribution in a novel tissue-chamber model in steers. The model accurately reflects interstitial compartments, showing delayed drug diffusion and varying protein binding effects.

Area of Science:

  • Pharmacokinetics
  • Biomedical Engineering
  • Veterinary Medicine

Background:

  • Subcutaneously implanted tissue chambers offer a model for studying drug distribution in interstitial spaces.
  • Characterizing the pharmacokinetic properties of such models is crucial for their validation and application in research.

Purpose of the Study:

  • To characterize the pharmacokinetics of a subcutaneously implanted tissue-chamber model in steers.
  • To evaluate the distribution of antipyrine and phenylbutazone into the chambers over time.
  • To assess the influx of endogenous molecules (urea, creatinine, albumin) to validate the model as an interstitial compartment.

Main Methods:

  • Thermoplastic tissue chambers were implanted in steers.
  • Intravenous administration of antipyrine and phenylbutazone followed by measurement of their concentrations in chamber fluid.

Related Experiment Videos

  • Measurement of endogenous urea, creatinine, and albumin influx into chambers.
  • Analysis using a compartmental model to describe drug diffusion.

    • Main Results:

    • Delayed diffusion of antipyrine and phenylbutazone into tissue chambers was observed and modeled.
    • Antipyrine distribution was greater than phenylbutazone, correlating with protein binding.
    • No significant effect of time on drug penetration into the chambers was found.
    • Rapid influx of urea and creatinine, and slow influx of albumin, confirmed the chambers as true interstitial compartments.

    Conclusions:

    • The subcutaneously implanted tissue-chamber model effectively mimics interstitial compartments.
    • The model demonstrates predictable drug distribution kinetics influenced by factors like protein binding.
    • This validated model can be utilized for pharmacokinetic studies in a large animal model.