A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects
Article first published online: 15 MAR 2013
© 2012 ViiV. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 75, Issue 4, pages 990–996, April 2013
How to Cite
Koteff, J., Borland, J., Chen, S., Song, I., Peppercorn, A., Koshiba, T., Cannon, C., Muster, H. and Piscitelli, S. C. (2013), 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, 75: 990–996. doi: 10.1111/j.1365-2125.2012.04440.x
- Issue published online: 15 MAR 2013
- Article first published online: 15 MAR 2013
- Accepted manuscript online: 20 AUG 2012 08:03AM EST
- Manuscript Accepted: 11 AUG 2012
- Manuscript Received: 14 MAY 2012
- Shionogi–ViiV Healthcare LLC
- creatinine clearance;
- dolutegravir (DTG;
- glomerular filtration rate;
- HIV integrase;
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.