The Universally Unrecognized Assumption in Predicting Drug Clearance and Organ Extraction Ratio

For almost a half‐century clearance concepts have been utilized in pharmacokinetics to understand the relationship between the dose administered and the time course of systemic concentrations to predict efficacy and safety, as well as how dosing should be modified in disease states. Various models o...

Full description

Saved in:
Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2018-03, Vol.103 (3), p.521-525
Main Authors: Benet, LZ, Liu, S, Wolfe, AR
Format: Article
Language:English
Subjects:
Algorithms
Data Interpretation, Statistical
Dose-Response Relationship, Drug
Humans
Liver - metabolism
Metabolic Clearance Rate
Models, Biological
Pharmaceutical Preparations - metabolism
Pharmacokinetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:For almost a half‐century clearance concepts have been utilized in pharmacokinetics to understand the relationship between the dose administered and the time course of systemic concentrations to predict efficacy and safety, as well as how dosing should be modified in disease states. Various models of organ clearance/elimination have been proposed and tested. Surprisingly, however, the theoretical basis for the appropriate data collection to test these models has never been evaluated. Here we show that in vivo data collection limitations and the extraction ratio concept itself are only consistent with the well‐stirred model of hepatic elimination. Evaluating measures of drug concentrations entering and leaving an organ will appear to best fit the well‐stirred model, since driving force concentrations within the organ of elimination cannot be measured.
ISSN:0009-9236
1532-6535
DOI:10.1002/cpt.802