BACKGROUND The hepatitis C virus(HCV) NS5A inhibitor ABT-267(ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450(paritaprevir, PTV), the CYP3A inhibitor ritonavir(r) and the non-nucleoside NS5B polymerase inhi...BACKGROUND The hepatitis C virus(HCV) NS5A inhibitor ABT-267(ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450(paritaprevir, PTV), the CYP3A inhibitor ritonavir(r) and the non-nucleoside NS5B polymerase inhibitor ABT-333(dasabuvir, DSV)(OBV/PTV/r + DSV) with or without ribavirin(RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1(GT1) infected patients. Patients with HCV who are considered "hard-to-cure" have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures.AIM To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials.METHODS Patients were ≥ 18 years old and chronically infected with HCV GT1(GT1a, GT1b or GT1a/1b). Patients were treatment-na?ve or previously failed a regimen including pegylated interferon/RBV +/-telaprevir, boceprevir, or simeprevir.One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/-RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment.RESULTS Many of the patients studied had comorbidities(44.2% hypertensive, 33.7%obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority(88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue(12%), headache(10%),insomnia(9%) and diarrhea(8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all(98%) patients were treatment compliant.CONCLUSION In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/-RBV is highly effective and tolerable and results in better mental and physical health following treatment.展开更多
We observed a sustained viral response(SVR) of ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin therapy, for 12 wk, in two cases with compensated liver cirrhosis and fully destroyed early hepatocellular carc...We observed a sustained viral response(SVR) of ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin therapy, for 12 wk, in two cases with compensated liver cirrhosis and fully destroyed early hepatocellular carcinoma(HCC). Patients were infected with hepatitis C virus(HCV) genotype 1b and were previous null responders/relapsers to interferon-alpha/ribavirin(IFN/RBV). There was a rapid suppression of HCV RNA to undetectable levels within the first two treatment weeks. SVR was achieved even after marked reduction of the RBV dose. The treatment was well tolerated. Both subjects experienced worsening of liver disease during therapy, in different patterns: severe, transient, predominantly direct hyperbilirubinemia without cytolysis(case 1) or progressive increase of aminotransferases(grade 4) without severe hyperbilirubinemia(case 2).Adverse events spontaneously resolved. The patients remained in a good clinical condition without hepatic decompensation. There was no re-occurrence of HCC. This is the first report for treatment of HCV cirrhosis after complete HCC destruction.展开更多
Ritonavir sulfate is a protease inhibitor widely used in the treatment of acquired immunodeficiency syndrome. In order to elucidate the inherent stability and sensitivity characteristics of ritonavir sulfate, it was i...Ritonavir sulfate is a protease inhibitor widely used in the treatment of acquired immunodeficiency syndrome. In order to elucidate the inherent stability and sensitivity characteristics of ritonavir sulfate, it was investigated under forced thermal and hydration stress conditions as recommended by the Inter- national Conference on Harmonization guidelines. In addition, competency of vibrational （infrared and Raman） spectroscopy was assessed to identify structural changes of the drug symbolizing its stress degradation. High performance liquid chromatography was used as a confirmatory technique for both thermal and hydration stress study, while thermogravimetric analysis]differential thermal analysis and atomic force microscopy substantiated the implementation of vibrational spectroscopy in this frame- work. The results exhibited high thermal stability of the drug as significant variations were observed in the diffuse reflectance infrared Fourier transform spectra only after the drug exposure to thermal radiations at 100 ℃. Hydration behavior of ritonavir sulfate was evaluated using Raman spectroscopy and the value of critical relative humidity was found to be 〉 67%. An important aspect of this study was to utilize vibrational spectroscopic technique to address stability issues of pharmacological molecules, not only for their processing in pharmaceutical industry, but also for predicting their shelf lives and suitable storage conditions.展开更多
基金an investigatorinitiated grant from AbbVie(B15-791)
文摘BACKGROUND The hepatitis C virus(HCV) NS5A inhibitor ABT-267(ombitasvir, OBV), the HCV NS4/4A protease inhibitor ABT-450(paritaprevir, PTV), the CYP3A inhibitor ritonavir(r) and the non-nucleoside NS5B polymerase inhibitor ABT-333(dasabuvir, DSV)(OBV/PTV/r + DSV) with or without ribavirin(RBV) is a direct-acting antiviral regimen approved in the United States and other major countries for the treatment of HCV in genotype 1(GT1) infected patients. Patients with HCV who are considered "hard-to-cure" have generally been excluded from registration trials due to rigorous study inclusion criteria, presence of comorbidities and previous treatment failures.AIM To investigate the efficacy of this regimen in HCV G1-infected patients historically excluded from clinical trials.METHODS Patients were ≥ 18 years old and chronically infected with HCV GT1(GT1a, GT1b or GT1a/1b). Patients were treatment-na?ve or previously failed a regimen including pegylated interferon/RBV +/-telaprevir, boceprevir, or simeprevir.One hundred patients were treated with the study drug regimen, which was administered for 12 or 24 wk +/-RBV according to GT1 subtype and presence/absence of cirrhosis. Patients were evaluated every 4 wk from treatment day 1 and at 4 and 12 wk after end-of-treatment.RESULTS Many of the patients studied had comorbidities(44.2% hypertensive, 33.7%obese, 20.2% cirrhotic) and 16% previously failed HCV treatment. Ninety-six patients completed study follow-up and 99% achieved 12-wk sustained virologic response. The majority(88.4%) of patients had undetectable HCV RNA by week 4. The most common adverse events were fatigue(12%), headache(10%),insomnia(9%) and diarrhea(8%); none led to treatment discontinuation. Physical and mental patient reported outcomes scores significantly improved after treatment. Almost all(98%) patients were treatment compliant.CONCLUSION In an all-comers HCV GT1 population, 12 or 24-wk of OBV/PTV/r + DSV +/-RBV is highly effective and tolerable and results in better mental and physical health following treatment.
文摘We observed a sustained viral response(SVR) of ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin therapy, for 12 wk, in two cases with compensated liver cirrhosis and fully destroyed early hepatocellular carcinoma(HCC). Patients were infected with hepatitis C virus(HCV) genotype 1b and were previous null responders/relapsers to interferon-alpha/ribavirin(IFN/RBV). There was a rapid suppression of HCV RNA to undetectable levels within the first two treatment weeks. SVR was achieved even after marked reduction of the RBV dose. The treatment was well tolerated. Both subjects experienced worsening of liver disease during therapy, in different patterns: severe, transient, predominantly direct hyperbilirubinemia without cytolysis(case 1) or progressive increase of aminotransferases(grade 4) without severe hyperbilirubinemia(case 2).Adverse events spontaneously resolved. The patients remained in a good clinical condition without hepatic decompensation. There was no re-occurrence of HCC. This is the first report for treatment of HCV cirrhosis after complete HCC destruction.
文摘Ritonavir sulfate is a protease inhibitor widely used in the treatment of acquired immunodeficiency syndrome. In order to elucidate the inherent stability and sensitivity characteristics of ritonavir sulfate, it was investigated under forced thermal and hydration stress conditions as recommended by the Inter- national Conference on Harmonization guidelines. In addition, competency of vibrational （infrared and Raman） spectroscopy was assessed to identify structural changes of the drug symbolizing its stress degradation. High performance liquid chromatography was used as a confirmatory technique for both thermal and hydration stress study, while thermogravimetric analysis]differential thermal analysis and atomic force microscopy substantiated the implementation of vibrational spectroscopy in this frame- work. The results exhibited high thermal stability of the drug as significant variations were observed in the diffuse reflectance infrared Fourier transform spectra only after the drug exposure to thermal radiations at 100 ℃. Hydration behavior of ritonavir sulfate was evaluated using Raman spectroscopy and the value of critical relative humidity was found to be 〉 67%. An important aspect of this study was to utilize vibrational spectroscopic technique to address stability issues of pharmacological molecules, not only for their processing in pharmaceutical industry, but also for predicting their shelf lives and suitable storage conditions.
