AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
RCT Entities:
AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Jan van Lunzen; Franco Maggiolo; José R Arribas; Aza Rakhmanova; Patrick Yeni; Benjamin Young; Jürgen K Rockstroh; Steve Almond; Ivy Song; Cindy Brothers; Sherene Min Journal: Lancet Infect Dis Date: 2011-10-20 Impact factor: 25.071
Authors: F Gaspari; N Perico; P Ruggenenti; L Mosconi; C S Amuchastegui; E Guerini; E Daina; G Remuzzi Journal: J Am Soc Nephrol Date: 1995-08 Impact factor: 10.121
Authors: Ann M Ginsberg; Martino W Laurenzi; Doris J Rouse; Karl D Whitney; Mel K Spigelman Journal: Antimicrob Agents Chemother Date: 2009-06-15 Impact factor: 5.191
Authors: James M Mikula; Maura M Manion; Frank Maldarelli; Lucila M Suarez; Jaha F Norman-Wheeler; Alex G Ober; Robin L Dewar; Jeffrey B Kopp; H Clifford Lane; Alice K Pau Journal: Antivir Ther Date: 2016-03-08
Authors: Matthew L Rizk; Robert Houle; Grace Hoyee Chan; Mike Hafey; Elizabeth G Rhee; Xiaoyan Chu Journal: Antimicrob Agents Chemother Date: 2013-12-02 Impact factor: 5.191
Authors: Michael T Eadon; Hongji Zhang; Todd C Skaar; Takashi Hato; Pierre C Dagher; Samir K Gupta; Zeruesenay Desta Journal: Antivir Chem Chemother Date: 2015-07-30