No clinically significant pharmacokinetic interactions between dolutegravir and daclatasvir in healthy adult subjects

BMC Infectious Diseases

Research Article

Timothy Eley¹  Shu-Pang Huang¹  Ivy H. Song²  Niki Arya²  Mike Choukour³  Jian Zong⁴  Ann M. Buchanan⁵  Brian Wynne⁵  Lisa L. Ross⁵ 

[1] Bristol-Myers Squibb, Princeton, NJ, USA;GlaxoSmithKline, Research Triangle Park, NC, USA;Parexel, Research Triangle Park, NC, USA;Pharstat, Research Triangle Park, NC, USA;ViiV Healthcare, Research Triangle Park, NC, USA;

关键词: Adult medicine;    Drug interactions;    Infectious disease;    Interactions;    Pharmacokinetics;   

DOI  :  10.1186/s12879-016-1629-5

 received in 2016-03-18, accepted in 2016-06-07,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundDaclatasvir (DCV) is an NS5A replication complex inhibitor recently approved for chronic hepatitis C virus treatment.MethodsTo 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.ResultsThe 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.ConclusionsDCV 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.Trial registrationRegistered on March 6, 2014 with ClinicalTrials.gov; registration number: NCT02082808 and as Study ID: 201102 on the ViiV Clinical Study Registry.

【 授权许可】

CC BY   
© The Author(s). 2016