Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir Tablets for Hepatitis C Virus Genotype 1 Infection

Klibanov, Olga M.; Gale, Stormi E; Santevecchi, Barbara A

doi:10.1177/1060028015570729

Cited by 48 publications

(51 citation statements)

References 51 publications

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“…In clinical studies, the regimen consisting of OBV/PTV/r + DSV ± RBV was highly efficacious to treat HCV GT1a or GT1b infection, including patients with compensated cirrhosis, liver transplant or human immunodeficiency virus 1 (HIV-1) co-infection. The observed SVR12 rate ranged from 92% to 100% (8,(12)(13)(14)(15)(16)(17)(18)(19).…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

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Direct-Acting Antivirals Ombitasvir / Paritaprevir / Ritonavir + Dasabuvir with or Without Ribavirin in Hepatitis C Virus (HCV) Genotype 1-Infected Treatment-Naive or Treatment-Experienced Patients with or Without Cirrhosis: Real-Life Experience in Lithuania and Latvia

et al. 2018

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Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

“…The combination of the NS5A inhibitor ombitasvir, the NS3/4A protease inhibitor paritaprevir boosted with ritonavir, and the NS5B polymerase inhibitor dasabuvir with or without ribavirin was approved to treat chronic HCV GT1 infection in the United Stated in December 2014 and in European Union in January 2015 (17,20).…”

Section: U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

Direct-Acting Antivirals Ombitasvir / Paritaprevir / Ritonavir + Dasabuvir with or Without Ribavirin in Hepatitis C Virus (HCV) Genotype 1-Infected Treatment-Naive or Treatment-Experienced Patients with or Without Cirrhosis: Real-Life Experience in Lithuania and Latvia

et al. 2018

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“…DSV CYP3A4, P-gp ve organik katyon transporter-1 molekülleri için substrattır ve karaciğer-de metabolize olur (72). Genotip 1 hastalarda PTV-RTV/OBV kombinasyonuyla birlikte, günde iki kez 250 mg'lık tablet şek-linde kullanılır (76).…”

Section: Sofosbuvir Ve Ledipasvirunclassified

“…Ancak orta derecede karaciğer yetmezliği (CTP-B) olan hastalarda bu kombinasyonun kullanılması önerilmemektedir. Ağır karaciğer yetmezliği olan (CTP-C) dekompanse sirozlu hastalarda PTV-RTV/OBV±DSV kullanımı kontrindikedir (76,77).…”

Section: Sofosbuvir Ve Ledipasvirunclassified

Management of Chronic Hepatitis C Virus Infection: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases-2017 Update

Aygen¹,

Demirtürk²,

Türker³

et al. 2017

Klimik Dergisi

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“…The most successful application of this strategy has been applied in the treatment of human immunodeficiency virus and hepatitis C virus infections whereby ritonavir ( Fig. 1) inhibits the clearance of antiviral therapeutics through inhibition of CYP3A4 (Kempf et al, 1995(Kempf et al, , 1997Koudriakova et al, 1998;Hirsch et al, 2008;Klibanov et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

N-Heterocyclic Carbene Capture by Cytochrome P450 3A4

et al. 2016

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Cytochrome P450 3A4 (CYP3A4) is the dominant P450 enzyme involved in human drug metabolism, and its inhibition may result in adverse interactions or, conversely, favorably reduce the systemic elimination rates of poorly bioavailable drugs. Herein we describe a spectroscopic investigation of the interaction of CYP3A4 with N-methylritonavir, an analog of ritonavir, widely used as a pharmacoenhancer. In contrast to ritonavir, the binding affinity of N-methylritonavir for CYP3A4 is pH-dependent. At pH ,7.4, the spectra are definitively type I, whereas at pH $7.4 the spectra have split Soret bands, including a red-shifted component characteristic of a P450-carbene complex. Variable-pH UV-visible spectroscopy binding studies with molecular fragments narrows the source of this pH dependence to its N-methylthiazolium fragment. The C2 proton of this group is acidic, and variable-pH resonance Raman spectroscopy tentatively assigns it a pK a of 7.4. Hence, this fragment of N-methylritonavir is expected to be readily deprotonated under physiologic conditions to yield a thiazol-2-ylidene, which is an N-heterocyclic carbene that has highaffinity for and is presumed to be subsequently captured by the heme iron. This mechanism is supported by time-dependent density functional theory with an active site model that accurately reproduces distinguishing features of the experimental UV-visible spectra of N-methylritonavir bound to CYP3A4. Finally, density functional theory calculations support that this novel interaction is as strong as the tightest-binding azaheterocycles found in P450 inhibitors and could offer new avenues for inhibitor development.

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Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir Tablets for Hepatitis C Virus Genotype 1 Infection

Cited by 48 publications

References 51 publications

Direct-Acting Antivirals Ombitasvir / Paritaprevir / Ritonavir + Dasabuvir with or Without Ribavirin in Hepatitis C Virus (HCV) Genotype 1-Infected Treatment-Naive or Treatment-Experienced Patients with or Without Cirrhosis: Real-Life Experience in Lithuania and Latvia

Direct-Acting Antivirals Ombitasvir / Paritaprevir / Ritonavir + Dasabuvir with or Without Ribavirin in Hepatitis C Virus (HCV) Genotype 1-Infected Treatment-Naive or Treatment-Experienced Patients with or Without Cirrhosis: Real-Life Experience in Lithuania and Latvia

Management of Chronic Hepatitis C Virus Infection: A Consensus Report of the Study Group for Viral Hepatitis of the Turkish Society of Clinical Microbiology and Infectious Diseases-2017 Update

N-Heterocyclic Carbene Capture by Cytochrome P450 3A4

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