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
PHARMACOGENOMICS | FUTURE MEDICINE LTD | Published : 2014
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 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.