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.