Endogenous Biomarkers to Assess Drug-Drug Interactions by Drug Transporters and Enzymes

Author(s): T. Thanga Mariappan*, Hong Shen, Punit Marathe.

Journal Name: Current Drug Metabolism

Volume 18 , Issue 8 , 2017

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Abstract:

Background: Drug-Drug Interactions (DDI) by modulation of drug transporters or drug metabolizing enzymes are common in multi-drug therapy. DDI potential of any new drug is assessed by conducting separate clinical studies using relevant probe substrates, which involves additional resource and cost. Recently, several endogenous compounds have been evaluated as substrates of transporters and enzymes that could be assessed as part of early clinical trials along with the assessment of drug pharmacokinetics, pharmacodynamics and safety studies. This enables an early readout on potential DDIs avoiding or minimally delaying the conduct of definitive DDI studies until later in clinical development.

Method: This review describes various endogenous biomarkers reported for drug transporters and metabolizing enzymes with their advantages and limitations.

Conclusion: Furthermore, the authors describe strategies to adopt while exploring a new endogenous biomarker, and factors to be considered in selection of biomarkers with the current challenges and opportunities.

Keywords: Endogenous biomarkers, transporters, enzymes, drug-drug interactions, inhibition, induction.

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Article Details

VOLUME: 18
ISSUE: 8
Year: 2017
Page: [757 - 768]
Pages: 12
DOI: 10.2174/1389200218666170724110818
Price: $58

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