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In vitro andin vivo evaluation of the tissue-to-blood partition coefficient for physiological pharmacokinetic models

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Abstract

An important parameter used in physiologically based pharmacokinetic models is the partition coefficient (Kp), which is defined as the ratio of tissue drug concentration to the concentration of drug in the emergent venous blood of the tissue. Since Kp is governed by reversible binding to protein and other constituents in blood and tissue, an attempt was made here to estimate the Kp values for a model drug ethoxybenzamide (EB) by means of in vitrobinding studies and to compare these Kp values to those obtained from in vivokinetic parameters observed following the administration of EB by two different routes, i.e., i.v. bolus injection and constant rate infusion. The Kp values obtained by using these three different methods were in reasonably good agreement suggesting that binding data obtained in vitrocan successfully be used to estimate in vivodistribution.

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Author notes

  1. Jiunn Huei Lin

    Present address: Drug Metabolism Section, Merck Sharp Dohme Research Laboratory, 19486, West Point, Pennsylvania

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, 113, Tokyo, Japan

    Jiunn Huei Lin, Yuichi Sugiyama & Manabu Hanano

  2. Department of Biopharmaceutics, Tokyo College of Pharmacy, Horinouchi, Hachioji, 192-03, Tokyo, Japan

    Shoji Awazu

Authors
  1. Jiunn Huei Lin
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  2. Yuichi Sugiyama
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  3. Shoji Awazu
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  4. Manabu Hanano
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Lin, J.H., Sugiyama, Y., Awazu, S. et al. In vitro andin vivo evaluation of the tissue-to-blood partition coefficient for physiological pharmacokinetic models. Journal of Pharmacokinetics and Biopharmaceutics 10, 637–647 (1982). https://doi.org/10.1007/BF01062545

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  • DOI: https://doi.org/10.1007/BF01062545

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