Journal
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
Volume 5, Issue 11, Pages 1369-1383Publisher
INFORMA HEALTHCARE
DOI: 10.1517/17425250903176421
Keywords
distribution; efficacy; pharmacokinetics; toxicity; transporters
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It has increasingly been recognized that few molecules move across the cell membrane without the assistance of transporter proteins. Large superfamilies of transporter proteins have been identified in every living cell, including microorganisms and mitochondria. This report reviews the role of transporters in physiology and pharmacology, and identifies where this may have an impact on drug efficacy and toxicity. This new understanding will require a fresh appreciation of pharmacokinetics and drug effects, as the current paradigms are based largely on the assumption that drug molecules have a reasonable unrestricted permeability across membranes. Rather than just focusing on clearance changes and central compartment pharmacokinetics, it will become increasingly necessary to examine the peripheral tissue distribution of drugs to more accurately predict drug efficacy and toxicity.
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