Abstract
Drug transporters play an important role in the absorption, distribution, excretion and toxicity of both endogenous and exogenous compounds. Transporters may act as physiological ‘gatekeepers’ in the regulation of the pharmacological and/or toxicological effects of drugs by limiting distribution to tissues responsible for their effect and/or toxicity. This review will first provide a brief outline of the characteristics of membrane bound drug transporter families and their respective roles in regulating drug pharmacokinetics. This background then provides the context for a discussion of the characterization of a drug candidate as a substrate, inhibitor and/or inducer of drug transporter(s), followed by an assessment of the in vitro and in vivo preclinical methods used in drug discovery and development for screening molecules to identify potential transporter interactions. Finally, specific examples of the translation of in vitro findings to the in vivo effects are discussed to link the current understanding of the impact of drug transporters to clinical pharmacology. Thus, the goal is to provide the drug discovery scientist with a cadre of concepts, strategies, and tools for ultimately making rational decisions in drug design and delivery resulting in the optimization of drug concentrations at the target of pharmacology.
Keywords: Drug transporters, drug-drug interaction, high throughput screening, pharmacokinetics, absorption, assay development, preclinical models, drug disposition
Combinatorial Chemistry & High Throughput Screening
Title: Evaluation of Drug Transporter Interactions in Drug Discovery and Development
Volume: 13 Issue: 2
Author(s): Yurong Lai, Kathleen E. Sampson and Jeffrey C. Stevens
Affiliation:
Keywords: Drug transporters, drug-drug interaction, high throughput screening, pharmacokinetics, absorption, assay development, preclinical models, drug disposition
Abstract: Drug transporters play an important role in the absorption, distribution, excretion and toxicity of both endogenous and exogenous compounds. Transporters may act as physiological ‘gatekeepers’ in the regulation of the pharmacological and/or toxicological effects of drugs by limiting distribution to tissues responsible for their effect and/or toxicity. This review will first provide a brief outline of the characteristics of membrane bound drug transporter families and their respective roles in regulating drug pharmacokinetics. This background then provides the context for a discussion of the characterization of a drug candidate as a substrate, inhibitor and/or inducer of drug transporter(s), followed by an assessment of the in vitro and in vivo preclinical methods used in drug discovery and development for screening molecules to identify potential transporter interactions. Finally, specific examples of the translation of in vitro findings to the in vivo effects are discussed to link the current understanding of the impact of drug transporters to clinical pharmacology. Thus, the goal is to provide the drug discovery scientist with a cadre of concepts, strategies, and tools for ultimately making rational decisions in drug design and delivery resulting in the optimization of drug concentrations at the target of pharmacology.
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Cite this article as:
Lai Yurong, Sampson E. Kathleen and Stevens C. Jeffrey, Evaluation of Drug Transporter Interactions in Drug Discovery and Development, Combinatorial Chemistry & High Throughput Screening 2010; 13 (2) . https://dx.doi.org/10.2174/138620710790596772
DOI https://dx.doi.org/10.2174/138620710790596772 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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