Document Detail

A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects.
MedLine Citation:
PMID:  22905856     Owner:  NLM     Status:  MEDLINE    
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.
Justin Koteff; Julie Borland; Shuguang Chen; Ivy Song; Amanda Peppercorn; Takaaki Koshiba; Courtney Cannon; Heather Muster; Stephen C Piscitelli
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Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of clinical pharmacology     Volume:  75     ISSN:  1365-2125     ISO Abbreviation:  Br J Clin Pharmacol     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-18     Completed Date:  2013-09-20     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  7503323     Medline TA:  Br J Clin Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  990-6     Citation Subset:  IM    
Copyright Information:
© 2012 ViiV. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
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MeSH Terms
Creatinine / urine*
Glomerular Filtration Rate / drug effects*
HIV Integrase Inhibitors / adverse effects,  pharmacology*
Heterocyclic Compounds, 3-Ring / adverse effects,  pharmacology*
Iohexol / pharmacokinetics
Middle Aged
Renal Plasma Flow / drug effects*
p-Aminohippuric Acid / pharmacokinetics
Reg. No./Substance:
0/HIV Integrase Inhibitors; 0/Heterocyclic Compounds, 3-Ring; 4419T9MX03/Iohexol; AYI8EX34EU/Creatinine; DKO1W9H7M1/dolutegravir; Y79XT83BJ9/p-Aminohippuric Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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