How Physicochemical Properties of Drugs Affect Their Metabolism and Clearance

Maria Karlgren, Christel A S Bergström

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

6 Citations (Scopus)

Abstract

In this chapter the transport proteins and enzymes of importance for drug clearance are discussed. The primary organ for drug metabolism is the liver and to reach the intracellular compartment of hepatocytes, orally administered drugs must cross both the intestinal wall and the cell membrane of the liver cells. Transport proteins present in the cellular membrane may facilitate or hinder the compounds crossing these cellular barriers and hence will influence to what extent compounds will reach the enzymes. Here, the enzymes and transport proteins of importance for drug clearance are discussed. The molecular features of importance for drug interactions with transport proteins and enzymes are analyzed and the possibility to predict molecular features vulnerable to enzymatic degradation is discussed. From detailed analysis of the current literature it is concluded that for interaction, both with transport proteins and enzymes, lipophilicity plays a major role. In addition to this property, molecular properties such as hydrogen bond acceptors and donors, charge, aromaticity and molecular size can be used to distinguish between routes of clearance.

Original languageEnglish
Title of host publicationNew Horizons in Predictive Drug Metabolism and Pharmacokinetics
EditorsAlan G. E. Wilson
PublisherThe Royal Society of Chemistry
Pages1-26
Number of pages26
Volume2016-January
Edition49
ISBN (Electronic) 9781782622376
ISBN (Print)9781849738286
DOIs
Publication statusPublished - 2016
Externally publishedYes

Publication series

NameRSC Drug Discovery Series
Number49
Volume2016-January
ISSN (Print)2041-3203

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