Journal article

Evaluation of the effect of UGT1A1 polymorphisms on dolutegravir pharmacokinetics

Shuguang Chen, Pamela St Jean, Julie Borland, Ivy Song, Astrid J Yeo, Stephen Piscitelli, Justin P Rubio



AIM: To evaluate potential pharmacogenetic effects of UGT1A1 polymorphisms on the pharmacokinetics (PK) of dolutegravir (Tivicay®; ViiV Healthcare, NC, USA), an HIV-1 integrase inhibitor. PATIENTS & METHODS: Analysis of pooled data from nine Phase I and II clinical studies was undertaken for 89 subjects receiving repeat dolutegravir 50 mg once daily (tablet formulation) who were genotyped for known UGT1A1 functional variants. RESULTS: Geometric mean ratio (92% CI) for subjects carrying low (*28/*28 and *28/*37) and reduced activity (*1/*6, *1/*28, *1/*37, *28/*36 and *36/*37) polymorphisms compared with subjects with normal activity (*1/*1 and *1/*36) showed decreased oral clearance (CL/F; 0..

View full abstract


Funding Acknowledgements

Funding for these studies was provided by ViiV Healthcare. All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. S Chen, P St Jean, J Borland, I Song, AJ Yeo, S Piscitelli and JP Rubio are employees of GlaxoSmithKline and own stock in Glaxo-SmithKline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.