Potential error in the measurement of tissue to blood distribution coefficients in physiological pharmacokinetic modeling

Residual tissue blood. I. Theoretical considerations

S. P. Khor, Michael Mayersohn

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Physiological pharmacokinetic models require the determination of tissue to blood distribution coefficients. A theoretical model has been developed and the resulting equations indicate that under certain conditions it is necessary to correct for the presence of drug in the residual blood remaining in the tissue. The potential error in ignoring this residual blood is expressed mathematically in terms of several important factors that include the anatomical features of the tissue (volume fractions of the blood, interstitial fluid, and cellular space) as well as the physicochemical properties of the drug (extent of binding in the blood and tissues). These theoretical considerations and resulting simulations have been applied to experimental literature data for several compounds (methotrexate, digoxin, and biperiden). We conclude that correction for the residual blood is necessary when the values of tissue to blood distribution coefficients are very small or large (relative to one) and when the volume fraction of the blood in tissue is substantial.

Original languageEnglish (US)
Pages (from-to)478-485
Number of pages8
JournalDrug Metabolism and Disposition
Volume19
Issue number2
StatePublished - 1991

Fingerprint

Pharmacokinetics
Blood
Tissue
Blood Volume
Biperiden
Volume fraction
Digoxin
Extracellular Fluid
Methotrexate
Pharmaceutical Preparations
Theoretical Models
Fluids

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

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abstract = "Physiological pharmacokinetic models require the determination of tissue to blood distribution coefficients. A theoretical model has been developed and the resulting equations indicate that under certain conditions it is necessary to correct for the presence of drug in the residual blood remaining in the tissue. The potential error in ignoring this residual blood is expressed mathematically in terms of several important factors that include the anatomical features of the tissue (volume fractions of the blood, interstitial fluid, and cellular space) as well as the physicochemical properties of the drug (extent of binding in the blood and tissues). These theoretical considerations and resulting simulations have been applied to experimental literature data for several compounds (methotrexate, digoxin, and biperiden). We conclude that correction for the residual blood is necessary when the values of tissue to blood distribution coefficients are very small or large (relative to one) and when the volume fraction of the blood in tissue is substantial.",
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