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Pharmacokinetic Interactions Between the HCV Protease Inhibitor Boceprevir and Ritonavir-Boosted HIV-1 Protease Inhibitors Atazanavir, Darunavir, and Lopinavir.
MedLine Citation:
PMID:  23155151     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background. Boceprevir represents a new treatment option for hepatitis C (HCV)-infected patients, including those with HCV/human immunodeficiency virus (HIV) coinfection; however, little is known about pharmacokinetic interactions between boceprevir and antiretroviral drugs.Methods. A randomized, open-label study to assess the pharmacokinetic interactions between boceprevir and ritonavir-boosted protease inhibitors (PI/r) was conducted in 39 healthy adults. Subjects received boceprevir (800 mg, three times daily) for 6 days and then received PI/r as follows: atazanavir (ATV) 300 mg once daily, lopinavir (LPV) 400 mg twice daily, or darunavir (DRV) 600 mg twice daily, each with ritonavir (RTV) 100 mg on days 10-31, plus concomitant boceprevir on days 25-31.Results. Boceprevir decreased the exposure of all PI/r, with AUC(0-last) geometric mean ratios (GMR [90% confidence interval]) of 0.65 (0.55-0.78) for ATV/r; 0.66 (0.60-0.72) for LPV/r, and 0.56 (0.51-0.61) for DRV/r. Coadministration with boceprevir decreased RTV AUC(τ) by 22%-36%. ATV/r did not significantly affect boceprevir exposure, but boceprevir AUC(τ) was reduced by 45% and 32% when coadministered with LPV/r and DRV/r, respectively. Overall, treatments were well tolerated with no unexpected adverse events.Conclusions. Concomitant administration of boceprevir with PI/r resulted in reduced exposures of PI and boceprevir. These drug-drug interactions may reduce the effectiveness of PI/r and/or boceprevir when coadministered.
Authors:
Ellen G J Hulskotte; Hwa-Ping Feng; Fengjuan Xuan; Marga G J A van Zutven; Michelle A Treitel; Eric A Hughes; Edward O'Mara; Stephen P Youngberg; John A Wagner; Joan R Butterton
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-15
Journal Detail:
Title:  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America     Volume:  -     ISSN:  1537-6591     ISO Abbreviation:  Clin. Infect. Dis.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9203213     Medline TA:  Clin Infect Dis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Merck Sharp & Dohme Corp., Oss, The Netherlands.
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