A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para‐aminohippurate clearance in healthy subjects

British Journal of Clinical Pharmacology - Tập 75 Số 4 - Trang 990-996 - 2013
Justin Koteff1, Julie Borland2, Shuguang Chen2, Ivy Song2, Amanda Peppercorn2, T Koshiba3, Courtney Cannon4, Heather Muster4, Stephen C. Piscitelli2
1ViiV Healthcare Research Triangle Park North Carolina USA
2GlaxoSmithKline, Research Triangle Park, North Carolina, USA
3Shionogi & Co., Ltd Osaka Japan
4DaVita Clinical Research, Minneapolis, Minnesota, USA

Tóm tắt

AimDolutegravir (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.MethodsSubjects 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.ResultsAll 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.ConclusionsThese 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.

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Thông tin xuất bản

British Journal of Clinical Pharmacology

Tập 75 Số 4

990-996

Thông tin tác giả