Theoretical consideration of drug distribution kinetics in a noneliminating organ: Comparison between a "homogeneous (well-stirred)" model and "nonhomogeneous (tube)" model

Tetsuya Terasaki, Yuichi Sugiyama, Tatsuji Iga, Yasufumi Sawada, Manabu Hanano

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Drug distribution kinetics in a noneliminating organ or tissue has been mathematically examined. The homogeneous (well-stirred) model regards the noneliminating organ or tissue as a homogeneous compartment in which the drug is equilibrated with that in the blood leaving the organ or tissue. The nonhomogeneous (tube) model views the noneliminating organ or tissue as comprising a number of parallel cylindrical tubes containing binding sites distributed homogeneously along these tubes. These two models are examined, considering the pseudo-distribution equilibrium phase after bolus injection and a linear binding condition. Although both models predict a similar tissue distribution under a variety of conditions, significant differences exist in the predictions of various pharmacokinetic parameters as a function of the drug distribution, such as blood flow, organ volume, slope of the terminal phase, and the tissue-to-blood partition coefficients. The predictability and limitations of these two models are explored. Distribution characteristics of the two models are also examined for adriamycin, actinomycin D, tetrachlorobiphenyl, hexachlorobiphenyl, digoxin, and ethoxybenzamide; no difference is observed. It is concluded that the assumption of a homogeneous (well-stirred) compartment is suitable for describing the drug distribution kinetics of these drugs.

Original languageEnglish
Pages (from-to)265-287
Number of pages23
JournalJournal of Pharmacokinetics and Biopharmaceutics
Volume13
Issue number3
DOIs
Publication statusPublished - 1985 Jun 1
Externally publishedYes

Keywords

  • drug distribution kinetics
  • homogeneous model
  • noneliminating organ
  • nonhomogeneous model
  • physiological pharmacokinetics
  • redistribution clearance
  • tissue-to-blood partition coefficient
  • tissue-to-plasma partition coefficient
  • tube model
  • well-stirred model

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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