PMID: 8964239May 1, 1996Paper

The tissue cage in dogs--a pharmacologic model for the representation of plasma and tissue kinetics

DTW. Deutsche tierärztliche Wochenschrift
R ScherklH H Frey

Abstract

Determination of pharmacokinetic data from plasma often is not sufficient in order to predict or to explain the clinical efficacy of drugs, e.g., in non steroidal antiinflammatory drugs (NSAID) with short elimination half lives in plasma a discrepancy appears between elimination half life and clinical effect. We have studied the tissue kinetics of a drug having a long elimination half life (naproxen) in comparison with phenylbutazone and flunixin, having a short elimination half life in dogs after oral application. Tissue fluid was obtained by using so called "tissue cages" implanted laterally in the neck. An inflammatory response was produced by injecting 1-2 ml of 2% carrageenan into the chamber. The drug concentrations were determined throughout the experiments both in plasma and tissue fluid. Naproxen concentrations (elimination half life of about 72 h in dogs) achieved equilibrium between tissue fluid and plasma concentration. In the case of phenylbutazone, concentration in tissue fluid declined with a definitely longer half life than in plasma and exceeded plasma concentrations after some hours. Flunixin concentrations in plasma and exudate attained equilibrium after 2-5 h. Of clinical importance is the finding that after...Continue Reading

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