Identification of Appropriate Endogenous Biomarker for Risk Assessment of Multidrug and Toxin Extrusion Protein-Mediated Drug-Drug Interactions in Healthy Volunteers.

ABSTRACT: Endogenous biomarkers are emerging to advance clinical drug-drug interaction (DDI) risk assessment in drug development. Twelve healthy subjects received a multidrug and toxin exclusion protein (MATE) inhibitor (pyrimethamine, 10, 25, and 75 mg) in a crossover fashion to identify an appropriate endogenous biomarker to assess MATE1/2-K-mediated DDI in the kidneys. Metformin (500 mg) was also given as reference probe drug for MATE1/2-K. In addition to the previously reported endogenous biomarker candidates (creatinine and N¹ -methylnicotinamide (1-NMN)), N¹ -methyladenosine (m¹ A) was included as novel biomarkers. 1-NMN and m¹ A presented as superior MATE1/2-K biomarkers since changes in their renal clearance (CL_r ) along with pyrimethami

SUBMITTER: Miyake T 

PROVIDER: S-EPMC7891601 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature