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

• Published in: BMC infectious diseases Vol. 16; no. 1; p. 347
• Main Authors: Ross, Lisa L., Song, Ivy H., Arya, Niki, Choukour, Mike, Zong, Jian, Huang, Shu-Pang, Eley, Timothy, Wynne, Brian, Buchanan, Ann M.
• Format: Journal Article
• Language: English
• Published: London BioMed Central 22.07.2016; BioMed Central Ltd
• Subjects: Adolescent; Adult; Aged; Analysis; Antiviral Agents - blood; Antiviral Agents - pharmacokinetics; Area Under Curve; Cross-Over Studies; Drug Administration Schedule; Drug Interactions; Female; Health aspects; Healthy Volunteers; Heterocyclic Compounds, 3-Ring - blood; Heterocyclic Compounds, 3-Ring - pharmacokinetics; HIV and co-infections; HIV Integrase Inhibitors - blood; HIV Integrase Inhibitors - pharmacokinetics; Humans; Imidazoles - blood; Imidazoles - pharmacokinetics; Infectious Diseases; Internal Medicine; Male; Medical Microbiology; Medicine; Medicine & Public Health; Middle Aged; Outcome Assessment (Health Care); Parasitology; Pharmacokinetics; Research Article; Tropical Medicine; Young Adult; Adult medicine; Infectious disease; Interactions; Pharmacokinetics; Drug interactions
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-016-1629-5

Background Daclatasvir (DCV) is an NS5A replication complex inhibitor recently approved for chronic hepatitis C virus treatment. Methods 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. Results The geometric least-squares mean ratios (90 % confidence intervals) of DCV area under the concentration-time curve over a dosing interval (AUC 0-τ ), maximum observed concentration (C max ), and concentration at the end of the dosing interval (C τ ) 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 AUC 0-τ , C max , and C τ by approximately 33, 29, and 45 %, respectively. Conclusions DCV plasma exposure was not meaningfully affected by DTG. Coadministration of DTG with DCV resulted in slight increases in DTG AUC 0-τ , C max , and C τ . 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 registration Registered on March 6, 2014 with ClinicalTrials.gov; registration number: NCT02082808 and as Study ID: 201102 on the ViiV Clinical Study Registry.