健康受试者参加降尿酸新药Ⅰ期临床试验致急性肾损伤的案例分析

Case study of acute kidney injury in phase I clinical trial of new drugs in healthy subjects

本研究的降尿酸新药YF120片为一种新型尿酸转运蛋白1抑制药,通过强效抑制近端肾小管尿酸重吸收,从而降低血清尿酸水平。本研究设低、中、高(5、10、20 mg)3个剂量组,每天1次,连续给药7 d。在试验过程中,低剂量组2例健康受试者连续服用试验药物(5 mg qd)2 d后出现急性肾损伤表现。研究者及时停药、对肾损伤原因进行分析并对症处理,最终2例受试者肾功能均恢复正常;该剂量组其余6例受试者在加强肾功能指标监测的情况下完成试验。根据低剂量试验结果,研究者建议停止多次给药的剂量爬坡。

Objective YF120,a novel uric acid transporter 1 inhibitor,can decrease plasma uric acid levels though potently inhibiting uric acid reabsorption in the proximal renal tubule.Subjects were assigned to three dose groups(5,10 and 20 mg),each subject was administered YF120 tablets once daily for 7 consecutive days.During the study,two subjects were reported acute kidney injury after 5 mg administration for 2 days.The investigators stopped drug administration immediately,analyzed the reason of this adverse event,and given symptomatic treatment.The two subjects’renal function returned to normal after the above processing.The remaining 6 subjects completed the administrations with strengthened monitoring of renal function indicators.Based on the results of the low-dose experiment,the investigators suggested stopping the dose escalation of multiple doses.