ViiV Healthcare, Research Triangle Park, North Carolina, USA.
Br J Clin Pharmacol. 2013 Apr;75(4):990-6. doi: 10.1111/j.1365-2125.2012.04440.x.
Dolutegravir (DTG; S/GSK1349572) is under clinical development as a once daily, unboosted integrase inhibitor for the treatment of HIV infection. The effect of DTG on glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and creatinine clearance (CLcr ) was evaluated in 34 healthy volunteers.
Subjects received DTG 50 mg (once daily or twice daily) or placebo for 14 days. GFR was measured by iohexol plasma clearance, ERPF was assessed by para-aminohippurate plasma clearance and CLcr was measured by 24 h urine collection.
All treatments were generally well tolerated. A modest decrease (10-14%) in CLcr was observed, consistent with clinical study observations. DTG 50 mg once daily and twice daily had no significant effect on GFR or ERPF compared with placebo over 14 days in healthy subjects.
These findings support in vitro data that DTG increases serum creatinine by the benign inhibition of the organic cation transporter 2, which is responsible for tubular secretion of creatinine.
多拉韦林（DTG；S/GSK1349572）是一种每日一次、无需增效的整合酶抑制剂，正在开发中用于治疗 HIV 感染。本研究旨在评估 DTG 对肾小球滤过率（GFR）、有效肾血浆流量（ERPF）和肌酐清除率（CLcr）的影响，共纳入 34 名健康志愿者。
受试者接受 DTG 50mg（每日一次或每日两次）或安慰剂治疗 14 天。通过碘海醇血浆清除率测量 GFR，通过对氨基马尿酸血浆清除率评估 ERPF，通过 24 小时尿液收集测量 CLcr。
所有治疗均具有良好的耐受性。与安慰剂相比，每日一次和每日两次服用 DTG 50mg 治疗 14 天后，CLcr 适度下降（10-14%），这与临床研究观察结果一致。在健康受试者中，DTG 50mg 每日一次或每日两次治疗与安慰剂相比，在 14 天内对 GFR 或 ERPF 无显著影响。
这些发现支持体外数据，即 DTG 通过良性抑制有机阳离子转运蛋白 2 增加血清肌酐，该蛋白负责肌酐的肾小管分泌。
