title: Ritonavir-boosted protease inhibitor based therapy: a new strategy in chronic hepatitis C therapy.
abstract: Chronic hepatitis C virus (HCV) infection is a worldwide health issue. All oral therapies are quickly replacing peg-interferon-based treatment regimens. Developing effective, well tolerated, treatments accessible for difficult to treat populations remains an unmet need. Ritonavir, an HIV-1 protease inhibitor, has pharmacokinetic properties that enhance the activity of concomitantly administered direct acting antivirals against HCV. Ritonavir inhibits Cytochrome P450 isozyme 3A4, diminishing first pass effect and hepatic metabolism, changing the pharmacokinetic parameters of Cytochrome P450 isozyme 3A4 substrates. When combined with the HCV protease inhibitor paritaprevir, ritonavir increases mean area under the curve, allowing once daily dosing. While Phase II and III clinical trials with ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir demonstrated high efficacy in those with HCV infection, drug-drug interactions warrant cautious use of ritonavir in specific patient populations. Consideration of the patients' full medication list is imperative due to the ubiquitous nature of the Cytochrome P450 isozyme 3A4 system.
authors.affiliation: University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Brayer
authors.forename: K Rajender
authors.initials: KR
authors.lastname: Reddy
mesh_terms: D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003521:Cyclopropanes; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011392:Proline / Q000031:analogs & derivatives; D011480:Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013449:Sulfonamides
chemical_list: D000998:Antiviral Agents; D003521:Cyclopropanes; D047029:Lactams, Macrocyclic; D047028:Macrocyclic Compounds; D011480:Protease Inhibitors; D013449:Sulfonamides; D011392:Proline; D019438:Ritonavir; C585405:paritaprevir
keywords: CYP3A4; direct-acting antiviral; hepatitis C; protease inhibitor; ritonavir