Development and implementation of urinary transporter biomarkers to facilitate assessment of drug-drug interaction.

Novel urinary biomarker evaluation approaches to support inhibition assessment for renal transporters (e.g., OCT2, multidrug and toxin extrusion proteins [MATEs]). Highly sensitive and robust hydrophilic interaction chromatography-MS/high-resolution MS assays, for urine and plasma, were developed and characterized to evaluate transporter biomarkers including N-methyladenosine and N-methylnicotinamide. The assays were simple and reliable with good selectivity and sensitivity, and successfully supported a clinical drug-drug interaction study with a drug candidate that presented inhibition of OCT2 and MATEs. The multiplexed assays enable a performance comparison, including biomarker specificity and sensitivity, that should increase the confidence in early clinical OCT2/MATEs drug-drug interaction risk assessment.