title: No clinically significant pharmacokinetic interactions between dolutegravir and daclatasvir in healthy adult subjects.
abstract: Daclatasvir (DCV) is an NS5A replication complex inhibitor recently approved for chronic hepatitis C virus treatment.
  
  
  
  To assess drug interactions between the HIV integrase strand transfer inhibitor dolutegravir (DTG) and DCV, subjects were randomized into 1 of 2 sequences in an open-label, 3-period, crossover study. Subjects received either DTG 50 mg once daily or DCV 60 mg once daily for 5 days in periods 1 and 2 and DTG 50 mg plus DCV 60 mg once daily for 5 days in period 3, with no washout between periods 2 and 3. Between periods 1 and 2, there was a washout period of at least 7 days.
  
  
  
  The geometric least-squares mean ratios (90 % confidence intervals) of DCV area under the concentration-time curve over a dosing interval (AUC0-τ), maximum observed concentration (Cmax), and concentration at the end of the dosing interval (Cτ) were 0.978 (0.831-1.15), 1.03 (0.843-1.25), and 1.06 (0.876-1.29), respectively, when DCV was administered with DTG compared with DCV alone. Compared with DTG alone, coadministration of DTG with DCV increased DTG AUC0-τ, Cmax, and Cτ by approximately 33, 29, and 45 %, respectively.
  
  
  
  DCV plasma exposure was not meaningfully affected by DTG. Coadministration of DTG with DCV resulted in slight increases in DTG AUC0-τ, Cmax, and Cτ. Accumulated safety and tolerability data in humans receiving DTG to date suggests this effect is not considered clinically significant. DTG and DCV can be coadministered without dose adjustment.
  
  
  
  Registered on March 6, 2014 with ClinicalTrials.gov; registration number: NCT02082808 and as Study ID: 201102 on the ViiV Clinical Study Registry.
authors.affiliation: ViiV Healthcare, Research Triangle Park, NC, USA. lisa.l.ross@viivhealthcare.com.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Ross
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Ivy H
authors.initials: IH
authors.lastname: Song
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: Niki
authors.initials: N
authors.lastname: Arya
authors.affiliation: Parexel, Research Triangle Park, NC, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Choukour
authors.affiliation: Pharstat, Research Triangle Park, NC, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zong
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Shu-Pang
authors.initials: SP
authors.lastname: Huang
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Eley
authors.affiliation: ViiV Healthcare, Research Triangle Park, NC, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Wynne
authors.affiliation: ViiV Healthcare, Research Triangle Park, NC, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Buchanan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002219:Carbamates; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D019428:HIV Integrase Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D064368:Healthy Volunteers; D006575:Heterocyclic Compounds, 3-Ring / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011759:Pyrrolidines; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult; D000099226:Dolutegravir
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D007093:Imidazoles; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D011759:Pyrrolidines; D014633:Valine; D000099226:Dolutegravir; C549273:daclatasvir
keywords: Adult medicine; Drug interactions; Infectious disease; Interactions; Pharmacokinetics