Current progress in identifying endogenous biomarker candidates for drug transporter phenotyping and their potential application to drug development

Abstract Drug transporters play important roles in the elimination of various compounds from the blood. Genetic variation and drug–drug interactions underlie the pharmacokinetic differences for the substrates of drug transporters. Some endogenous substrates of drug transporters have emerged as biomarkers to assess differences in drug transporter activity—not only in animals, but also in humans. Metabolomic analysis is a promising approach for identifying such endogenous substrates through their metabolites. The appropriateness of metabolites is supported by studies in vitro and in vivo, both in animals and through pharmacogenomic or drug–drug interaction studies in humans. This review summarizes current progress in identifying such endogenous biomarkers and applying them to drug transporter phenotyping.