Comprehensive analysis of endogenous compounds applicable to in vivo evaluation of drugs transporters

本研究的目的是确定内源性探针，适用于体内评价药物转运体在人体内的活性。在参与药物相互作用研究的健康受试者的生物样本中，研究了血浆或尿液中与转运蛋白活性相关的内源性探针。我们可以证明硫胺素是一个探针肾有机阳离子转运体（MATE）， 6 -羟基皮质醇是一个探针肾有机阴离子转运体（OAT3）。它们的肾脏清除率通过抑制剂的施用显着降低，表明它们在评估涉及这些转运蛋白的药物-药物相互作用方面的有用性。

The purpose of this study is to identify the endogenous probes that are applicable to in vivo evaluation of drug transporter activities in humans. The endogenous probes, the plasma or urinary excretion of which were associated with the transporter activities, were investigated in the biological samples from the healthy subjects who had been enrolled in the drug interaction studies. We could demonstrate that thiamine is a probe renal organic cation transporter (MATE), that 6beta-hydroxycortisol is a probe for renal organic anion transporter (OAT3). Their renal clearances were significantly reduced by the administration of inhibitors, showing their usefulness in the evaluation of drug-drug interactions involving these transporters.