Combination Of Grazoprevir Research Articles

Eradication of hepatitits C virus in patient with cryoglobulinemic vasculitis and mutations D168E, L31V

The case of chronic hepatitis C 1b genotype with grade 3 fibrosis according to Metavir, complicated by the development of mixed type III cryoglobulinemia, cryoglobulinemic vasculitis with damage to the skin vessels of the skin (hemorrhagic vasculitis), and the liver (alternatively proliferative vasculitis) is demonstrated. The introduction of daclatasvir + asunaprevir was virologically unsuccessful: mutations D168E and L31V were detected against the background of a virological breakthrough. A repeated course of antiviral therapy with the combination of Grazoprevir + Elbasvir in combination with sofosbuvir led to a stable virologic response, partial immunological and clinical remission.

Stability indicating validated RP-HPLC method for Simultaneous estimation of Elbasvir and Grazopravir in Bulk and Pharmaceutical Dosage form

Elbasvir a NS5A inhibitor is used in combination of Grazoprevir (NS3/4A protease inhibitor) for the treatment of chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV) under the trade name Zepatiar®. A stability indicating reverse phase HPLC method was developed and validated for the determination of Elbasvir and Grazoprevir in tablet dosage form. A waters Alliance HPLC with Zorbax eclipse XDB C18 (250 x 4.6 mm) 3.5μ columnwas used for chromatographic separation. A mobile phase consisting of potassium dihydrogen phosphate buffer pH adjusted to 4.0: acetonitrile (40: 60v/v) with a flow rate of 1.0 mL/min was used, the UV detection was carried out at 260 nm. The established method was linear, accurate and precise over the range of 12.5 to 75 μg/mL with a regression equation of Y=20782X+2849.4 and correlation coefficient of 0.9995for elbasvir and linear over the range of 25–150 μg/mL with a regression equation of Y=14897X+20611 and correlation coefficient of 0.9992for Grazoprevir. The validated method demonstrated high sensitivity, accuracy, precision, selectivity and robustness. The method demonstrated high selectivity in presence of degradants produced during the stress conditions when Elbasvir and Grazoprevir were subjected to acid, alkali, oxidation, thermal and photolytic degradation.

Development and validation of a highly sensitive second derivative synchronous fluorescence spectroscopic method for the simultaneous determination of elbasvir and grazoprevir in pharmaceutical preparation and human plasma

Elbasvir and grazoprevir combination has been newly approved for the treatment of patients infected with hepatitis C virus.

Grazoprevir + elbasvir for the treatment of hepatitis C virus infection

ABSTRACTIntroduction: Hepatitis C virus (HCV)-related liver disease is a cause of significant morbidity and mortality worldwide. Currently, direct-acting antiviral drugs (DAAs) are associated with an increased sustained virologic response (SVR) and are the gold standard for treating HCV infection.Areas covered: The new combination of grazoprevir, an inhibitor of HCV NS3/4A, and elbasvir, an inhibitor of HCV NS5A, once daily will be available for the treatment of HCV infection. This combination therapy has a high efficacy in HCV genotype 1 and 4 infections, inducing a SVR up to 95%, even in difficult to treat patients such as cirrhotic, HIV co-infected, or dialysis-dependent patients, and patients with stage 4–5 chronic kidney disease or those who failed previous therapy. The safety of grazoprevir combined with elbasvir is very good and without significant adverse effects in phase 2 or 3 studies. For patients who failed prior DAA therapy, in vitro and in vivo studies showed that the grazoprevir and elbasvir combination is fully active against resistance to NS3/4A protease inhibitors. Resistance to NS5B inhibitors is least susceptible to grazoprevir or elbasvir.Expert opinion: This new combination of gazoprevir with elbasvir offers an opportunity to cure HCV infection with short interferon-free therapy, even in difficult to treat patients.

The Combination of Grazoprevir, a Hepatitis C Virus (HCV) NS3/4A Protease Inhibitor, and Elbasvir, an HCV NS5A Inhibitor, Demonstrates a High Genetic Barrier to Resistance in HCV Genotype 1a Replicons.

The selection of resistance-associated variants (RAVs) against single agents administered to patients chronically infected with hepatitis C virus (HCV) necessitates that direct-acting antiviral agents (DAAs) targeting multiple viral proteins be developed to overcome failure resulting from emergence of resistance. The combination of grazoprevir (formerly MK-5172), an NS3/4A protease inhibitor, and elbasvir (formerly MK-8742), an NS5A inhibitor, was therefore studied in genotype 1a (GT1a) replicon cells. Both compounds were independently highly potent in GT1a wild-type replicon cells, with 90% effective concentration (EC90) values of 0.9 nM and 0.006 nM for grazoprevir and elbasvir, respectively. No cross-resistance was observed when clinically relevant NS5A and NS3 RAVs were profiled against grazoprevir and elbasvir, respectively. Kinetic analyses of HCV RNA reduction over 14 days showed that grazoprevir and elbasvir inhibited prototypic NS5A Y93H and NS3 R155K RAVs, respectively, with kinetics comparable to those for the wild-type GT1a replicon. In combination, grazoprevir and elbasvir interacted additively in GT1a replicon cells. Colony formation assays with a 10-fold multiple of the EC90 values of the grazoprevir-elbasvir inhibitor combination suppressed emergence of resistant colonies, compared to a 100-fold multiple for the independent agents. The selected resistant colonies with the combination harbored RAVs that required two or more nucleotide changes in the codons. Mutations in the cognate gene caused greater potency losses for elbasvir than for grazoprevir. Replicons bearing RAVs identified from resistant colonies showed reduced fitness for several cell lines and may contribute to the activity of the combination. These studies demonstrate that the combination of grazoprevir and elbasvir exerts a potent effect on HCV RNA replication and presents a high genetic barrier to resistance. The combination of grazoprevir and elbasvir is currently approved for chronic HCV infection.

Grazoprevir and Elbasvir: A Second-Generation Protease Inhibitor and a Second-Generation NS5A Inhibitor in a Combination Regimen for Treatment of Chronic Hepatitis C

ABSTRACT The emergence of direct acting antivirals against HCV infection has provided the opportunity for interferon free, all oral treatments for HCV infection in patients with HCV genotype 1 (GT1). This review describes the current data on the combination of grazoprevir and elbasvir, a second-generation NS3/4A inhibitor and a second-generation NS5A inhibitor, respectively. The regimen has shown promising results in Phase II trials in patients with GT1 with response rates >90%, even in patient groups that have been challenging to treat, such as patients with cirrhosis, HIV co-infection and previous null responders to treatment with pegylated IFN-α + ribavirin. Grazoprevir + elbasvir treatment is well tolerated. Phase III trials and trials including infections with GT2–4 + 6 are ongoing.

The Next Single-Pill HCV Regimen?

Work continues in the effort to develop a core set of hepatitis C virus (HCV) infection treatment regimens that require no more than 12 weeks of therapy, are effective in all genotypes, and are not only interferon-free, but also ribavirin-free. In the current industry-funded, phase III trial, investigators assessed the efficacy of a fixed-dose combination of grazoprevir (an NS3/4A protease inhibitor; 100 mg) …