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

Br J Clin Pharmacol. 2013 Apr;75(4):990-6. doi: 10.1111/j.1365-2125.2012.04440.x.


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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Creatinine / urine*
  • Female
  • Glomerular Filtration Rate / drug effects*
  • HIV Integrase Inhibitors / adverse effects
  • HIV Integrase Inhibitors / pharmacology*
  • Heterocyclic Compounds, 3-Ring / adverse effects
  • Heterocyclic Compounds, 3-Ring / pharmacology*
  • Humans
  • Iohexol / pharmacokinetics
  • Male
  • Middle Aged
  • Oxazines
  • Piperazines
  • Pyridones
  • Renal Plasma Flow / drug effects*
  • p-Aminohippuric Acid / pharmacokinetics


  • HIV Integrase Inhibitors
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • Iohexol
  • Creatinine
  • dolutegravir
  • p-Aminohippuric Acid