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Transporters And Their Impact On Drug Disposition

Paul M Beringer, Richard L Slaughter

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OBJECTIVE: To review the recent advances in knowledge about human transporters and their effect on drug disposition. DATA SOURCES: A MEDLINE search (1996–March 2005) was performed to identify pertinent literature on human transporters and their impact on drug disposition. Additional articles were identified from a manual search of the references of retrieved articles. STUDY SELECTION AND DATA EXTRACTION: Based on the identified studies, data were extracted on the impact of transporters on drug absorption, distribution, and elimination. DATA SYNTHESIS: The pharmacokinetic disposition of drugs is known to be influenced by metabolic enzymes, kidney function, and transporters. Recent research on human transporters has greatly advanced our understanding of their diversity and importance in drug disposition. In particular, members of the multidrug resistance family of transporters (MDR, MRP) are present in organs and tissues throughout the body and are known to significantly affect the absorption, distribution, and elimination of commonly prescribed drugs. A growing number of studies now demonstrate that alterations in transporter function as a result of drug interactions or genetic polymorphisms may explain a significant portion of the variability in treatment response for certain drugs. CONCLUSIONS: Human transporters contribute significantly to the pharmacokinetic disposition of drugs. Knowledge of substrates, inducers, and inhibitors of these transporters is necessary to ensure optimal patient outcomes.