RT Journal Article
SR Electronic
T1 Potential error in the measurement of tissue to blood distribution coefficients in physiological pharmacokinetic modeling. Residual tissue blood. I. Theoretical considerations.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 478
OP 485
VO 19
IS 2
A1 S P Khor
A1 M Mayersohn
YR 1991
UL http://dmd.aspetjournals.org/content/19/2/478.abstract
AB 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.