1. Assessment of drug interaction potential between the HCV direct-acting antiviral agents elbasvir/grazoprevir and the HIV integrase inhibitors raltegravir and dolutegravir.
- Author
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Feng HP, Guo Z, Ross LL, Fraser I, Panebianco D, Jumes P, Fandozzi C, Caro L, Talaty J, Ma J, Mangin E, Huang X, Marshall WL, Butterton JR, Iwamoto M, and Yeh WW
- Subjects
- Adult, Amides, Antiretroviral Therapy, Highly Active, Antiviral Agents administration & dosage, Antiviral Agents adverse effects, Antiviral Agents pharmacokinetics, Benzofurans administration & dosage, Benzofurans adverse effects, Benzofurans pharmacokinetics, Benzofurans therapeutic use, Carbamates, Chromatography, Liquid, Cyclopropanes, Drug Monitoring, Drug Therapy, Combination, Female, HIV Infections virology, HIV Integrase Inhibitors administration & dosage, HIV Integrase Inhibitors adverse effects, HIV Integrase Inhibitors pharmacokinetics, Hepatitis C virology, Heterocyclic Compounds, 3-Ring administration & dosage, Heterocyclic Compounds, 3-Ring adverse effects, Heterocyclic Compounds, 3-Ring pharmacokinetics, Heterocyclic Compounds, 3-Ring therapeutic use, Humans, Imidazoles administration & dosage, Imidazoles adverse effects, Imidazoles pharmacokinetics, Imidazoles therapeutic use, Male, Mass Spectrometry, Middle Aged, Oxazines, Piperazines, Pyridones, Quinoxalines administration & dosage, Quinoxalines adverse effects, Quinoxalines pharmacokinetics, Quinoxalines therapeutic use, Raltegravir Potassium administration & dosage, Raltegravir Potassium adverse effects, Raltegravir Potassium therapeutic use, Sulfonamides, Treatment Outcome, Young Adult, Antiviral Agents therapeutic use, Coinfection drug therapy, Drug Interactions, HIV Infections drug therapy, HIV Integrase Inhibitors therapeutic use, Hepatitis C drug therapy
- Abstract
Background: Elbasvir/grazoprevir is a once-daily fixed-dose combination therapy for the treatment of chronic HCV infection, including HCV/HIV coinfection., Objectives: To evaluate the pharmacokinetic interaction of elbasvir and grazoprevir with raltegravir or dolutegravir., Methods: Three open-label trials in healthy adult participants were conducted. In the raltegravir trials, participants received a single dose of raltegravir 400 mg, a single dose of elbasvir 50 mg or grazoprevir 200 mg, and raltegravir with either elbasvir or grazoprevir. In the dolutegravir trial, participants received a single dose of dolutegravir 50 mg alone or co-administered with once-daily elbasvir 50 mg and grazoprevir 200 mg., Results: The raltegravir AUC0-∞ geometric mean ratio (GMR) (90% CI) was 1.02 (0.81-1.27) with elbasvir and 1.43 (0.89-2.30) with grazoprevir. Dolutegravir AUC0-∞ GMR (90% CI) was 1.16 (1.00-1.34) with elbasvir and grazoprevir. The elbasvir AUC0-∞ GMR (90% CI) was 0.81 (0.57-1.17) with raltegravir and 0.98 (0.93-1.04) with dolutegravir. The grazoprevir AUC0-24 GMR (90% CI) was 0.89 (0.72-1.09) with raltegravir and 0.81 (0.67-0.97) with dolutegravir., Conclusions: Elbasvir or grazoprevir co-administered with raltegravir or dolutegravir resulted in no clinically meaningful drug-drug interactions and was generally well tolerated. These results support the assertion that no dose adjustments for elbasvir, grazoprevir, raltegravir or dolutegravir are needed for co-administration in HCV/HIV-coinfected people., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2019
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