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https://www.readbyqxmd.com/read/28334528/why-prodrugs-and-propesticides-succeed
#1
John E Casida
What are the advantages of bioactivation in optimizing drugs and pesticides? Why are there so many prodrugs and propesticides? These questions are examined here by considering compounds selected on the basis of economic value or market success. The 100 major drugs and 90 major pesticides are divided into ones acting directly and those definitely or possibly requiring bioactivation. Established or candidate prodrugs accounted for 19% of the total drug sales with corresponding values of 20, 37 and 17% for proinsecticides, proherbicides and profungicides...
March 23, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28332272/clinical-evaluation-of-sofosbuvir-ledipasvir-in-chronic-hepatitis-c-genotype-1-with-and-without-prior-daclatasvir-asnaprevir-therapy
#2
Etsuko Iio, Noritomo Shimada, Koichi Takaguchi, Tomonori Senoh, Yuichiro Eguchi, Masanori Atsukawa, Akihito Tsubota, Hiroshi Abe, Keizo Kato, Atsunori Kusakabe, Tomokatsu Miyaki, Kentaro Matsuura, Kayoko Matsunami, Noboru Shinkai, Kei Fujiwara, Shunsuke Nojiri, Yasuhito Tanaka
AIM: This study explored treatment outcomes of sofosbuvir (SOF)/ledipasvir (LDV) therapy for chronic hepatitis C patients with and without prior daclatasvir (DCV)/asunaprevir (ASV) therapy. METHODS: Overall, 530 Japanese patients who were infected with hepatitis C virus genotype 1 received SOF/LDV therapy for 12 weeks, and resistance-associated variants (RAVs) in the HCV NS5A and NS5B regions were assessed at baseline and virological relapse by direct sequencing...
March 22, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28330530/spectrophotometric-methods-for-simultaneous-determination-of-sofosbuvir-and-ledipasvir-harvoni-tablet-comparative-study-with-two-generic-products
#3
Nisreen F Abo-Talib, Mohamed R El-Ghobashy, Marwa H Tammam
Sofosbuvir and ledipasvir are the first drugs in a combination pill to treat chronic hepatitis C virus. Simple, sensitive, and rapid spectrophotometric methods are presented for the determination of sofosbuvir and ledipasvir in their combined dosage form. These methods were based on direct measurement of ledipasvir at 333 nm (due to the lack of interference of sofosbuvir) over a concentration range of 4.0–14.0 μg/mL, with a mean recovery of 100.78 ± 0.64%. Sofosbuvir was determined, without prior separation, by third-derivative values at 281 nm; derivative ratio values at 265...
February 10, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28329914/ginsenoside-rg3-restores-hepatitis-c-virus-induced-aberrant-mitochondrial-dynamics-and-inhibits-virus-propagation
#4
Seong-Jun Kim, Jae Young Jang, Eun-Jung Kim, Eun Kyung Cho, Dae Gyun Ahn, Chonsaeng Kim, Han Seul Park, Soung Won Jeong, Sae Hwan Lee, Sang Gyune Kim, Young Seok Kim, Hong Soo Kim, Boo Sung Kim, Ji-Hyung Lee, Aleem Siddiqui
Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their treatment of patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine and other conditions, which may be linked to mitochondrial dysfunction. Here we show that clinically prescribed DAAs, including Sofosbuvir, affect mitochondrial dynamics...
March 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28329053/sofosbuvir-plus-ribavirin-without-interferon-for-treatment-of-acute-hepatitis-c-virus-infection-in-hiv-1-infected-individuals-swift-c
#5
Susanna Naggie, Kristen M Marks, Michael Hughes, Daniel S Fierer, Christine Macbrayne, Arthur Kim, Kimberly Hollabaugh, Jhoanna Roa, Bill Symonds, Diana M Brainard, John G McHutchison, Marion G Peters, Jennifer J Kiser, Raymond Chung
Background.: Historically, acute hepatitis C virus (HCV) infection was treated with shorter durations of interferon-containing therapies. In the era of direct-acting antivirals (DAAs), it is unclear whether the efficacy of treatment achieved in chronic infection can be maintained with abbreviated courses of therapy during the acute phase. Methods.: The sofosbuvir-containing regimens without interferon for treatment of acute HCV in HIV-1 infected individuals (SWIFT-C) is an open-label, 2-cohort clinical trial in which the first cohort assessed for the safety and efficacy of 12 weeks of sofosbuvir plus ribavirin for the treatment of acute HCV infection in participants with chronic human immunodeficiency virus type 1 (HIV-1) infection...
February 27, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28328620/ledipasvir-and-sofosbuvir-combination-for-hepatitis-c-virus-infection-in-three-patients-aged-85-years-and-older
#6
Fanpu Ji, Changyin Tian, Zongfang Li, Hong Deng, Mindie H Nguyen
No abstract text is available yet for this article.
March 21, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28327633/cardiac-drug-drug-interaction-between-hcv-ns5b-pronucleotide-inhibitors-and-amiodarone-is-determined-by-their-specific-diastereochemistry
#7
Armando Lagrutta, Christopher P Regan, Haoyu Zeng, John P Imredy, Kenneth Koeplinger, Pierre Morissette, Liping Liu, Gordon Wollenberg, Christopher Brynczka, José Lebrón, Joseph DeGeorge, Frederick Sannajust
Severe bradycardia/bradyarrhythmia following coadministration of the HCV-NS5B prodrug sofosbuvir with amiodarone was recently reported. Our previous preclinical in vivo experiments demonstrated that only certain HCV-NS5B prodrugs elicit bradycardia when combined with amiodarone. In this study, we evaluate the impact of HCV-NS5B prodrug phosphoramidate diastereochemistry (D-/L-alanine, R-/S-phosphoryl) in vitro and in vivo. Co-applied with amiodarone, L-ala,SP prodrugs increased beating rate and decreased beat amplitude in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), but D-ala,RP produgs, including MK-3682, did not...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28321163/optimizing-hepatitis-c-virus-treatment-through-pharmacist-interventions-identification-and-management-of-drug-drug-interactions
#8
Jacob A Langness, Matthew Nguyen, Amanda Wieland, Gregory T Everson, Jennifer J Kiser
AIM: To quantify drug-drug-interactions (DDIs) encountered in patients prescribed hepatitis C virus (HCV) treatment, the interventions made, and the time spent in this process. METHODS: As standard of care, a clinical pharmacist screened for DDIs in patients prescribed direct acting antiviral (DAA) HCV treatment between November 2013 and July 2015 at the University of Colorado Hepatology Clinic. HCV regimens prescribed included ledipasvir/sofosbuvir (LDV/SOF), paritaprevir/ritonavir/ombitasvir/dasabuvir (OBV/PTV/r + DSV), simeprevir/sofosbuvir (SIM/SOF), and sofosbuvir/ribavirin (SOF/RBV)...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28320588/herpes-zoster-reactivation-in-patients-with-chronic-hepatitis-c-under-treatment-with-directly-acting-antiviral-agents-a-case-series
#9
Mohamed El Kassas, Mohamed Naguib Wifi, Reem Mahdy, Shimaa Afify, Enas Hafez, Yasmeen Abd El Latif, Marwa Ezzat, Adel El Tahan, Naglaa Youssef, Gamal Esmat
We report a series of cutaneous Herpes Zoster (HZ) reactivation cases in patients with hepatitis C virus (HCV) infection treated with directly acting antiviral (DAA) agents. Five cases were detected among 2133 treated patients with DAAs at one of the specialized viral hepatitis treatment centers in Egypt. A control group including 2300 age and sex matched HCV patients who were previously treated with pegylated interferon and ribavirin did not show any HZ reactivation reports while on treatment. None of cases had an evidence of immunosuppression or a risk factor for HZ reactivation...
March 17, 2017: Arab Journal of Gastroenterology: the Official Publication of the Pan-Arab Association of Gastroenterology
https://www.readbyqxmd.com/read/28315983/retreatment-with-sofosbuvir-ledipasvir-and-add-on-ribavirin-for-patients-who-failed-daclatasvir-and-asunaprevir-combination-therapy
#10
Goki Suda, Koji Ogawa, Yoshiya Yamamoto, Masaki Katagiri, Ken Furuya, Kenichi Kumagai, Jun Konno, Megumi Kimura, Naoki Kawagishi, Masatsugu Ohara, Machiko Umemura, Jun Ito, Takaaki Izumi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Akihito Tsubota, Noritomo Shimada, Etsuko Iio, Yasuhito Tanaka, Naoya Sakamoto
BACKGROUND: The optimal retreatment regimen for patients with hepatitis C virus (HCV) infection who failed interferon-free, direct-acting antiviral (DAA) therapy is undetermined. In this study, we aimed to evaluate the efficacy and safety of 12-week retreatment with ledipasvir (LDV) and sofosbuvir (SOF) with add-on ribavirin (RBV) for patients who previously failed to respond to HCV-NS5A inhibitor, daclatasvir (DCV), and HCV-NS3 inhibitor, asunaprevir (ASV), therapy. METHODS: This multicenter, prospective study enrolled 15 patients with genotype-1 HCV infection who failed DCV/ASV combination therapy...
March 18, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28295923/effect-of-viral-suppression-on-hepatic-venous-pressure-gradient-in-hepatitis-c-with-cirrhosis-and-portal-hypertension
#11
Nezam Afdhal, Gregory T Everson, Jose Luis Calleja, Geoffrey W McCaughan, Jaime Bosch, Diana M Brainard, John G McHutchison, Shampa De-Oertel, Di An, Michael Charlton, Rajender K Reddy, Tarik Asselah, Edward Gane, Michael P Curry, Xavier Forns
BACKGROUND&AIMS: Portal hypertension is a predictor of liver-related clinical events and mortality in patients with hepatitis C and cirrhosis. The effect of interferon-free hepatitis C treatment on portal pressure is unknown. METHODS: Fifty patients with Child-Pugh-Turcotte (CPT) A and B cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] >6 mmHg) were randomized to receive 48 weeks of open-label sofosbuvir plus ribavirin at Day 1 or after a 24-week observation period...
March 10, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28294645/cost-effectiveness-of-combination-daclatasvir-sofosbuvir-for-the-treatment-of-genotype-3-chronic-hepatitis-c-infection-in-the-united-states
#12
Catherine Saint-Laurent Thibault, Divya Moorjaney, Michael L Ganz, Bruce Sill, Shalini Hede, Yong Yuan, Boris Gorsh
BACKGROUND: A phase III trial evaluated the efficacy and safety of Daklinza (daclatasvir or DCV) in combination with sofosbuvir (SOF) for treatment of genotype (GT) 3 hepatitis C virus (HCV) patients. AIM: This study evaluated the cost-effectiveness of DCV+SOF versus SOF in combination with ribavirin (RBV) over a 20-year time horizon from the payer perspective in the United States (US). METHODS: A published Markov model was adapted to reflect US demographic characteristics, treatment patterns, costs of drug acquisition, monitoring, disease and adverse event management, and mortality risks...
March 15, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28288791/efficacy-and-safety-of-sofosbuvir-plus-daclatasvir-for-treatment-of-hcv-associated-cryoglobulinemia-vasculitis
#13
David Saadoun, Stanislas Pol, Yasmina Ferfar, Laurent Alric, Christophe Hezode, Si Nafa Si Ahmed, Luc de Saint Martin, Cloé Comarmond, Anne Sophie Bouyer, Lucile Musset, Thierry Poynard, Matthieu Resche Rigon, Patrice Cacoub
Circulating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in about 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct acting antiviral drugs in these patients. We performed open-label, prospective, multi-center study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas...
March 10, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28287204/-biliary-and-kidney-lithiasis-during-treatment-with-daclatasvir-sofosbuvir-ribavirin-and-atazanavir-ritonavir-abacavir-lamivudine-in-an-hiv-hcv-genotype-4-infected-patient-a-case-report
#14
Andrea Vavassori, Paola Lanza, Ilaria Izzo, Salvatore Casari, Silvia Odolini, Serena Zaltron, Elena Festa, Francesco Castelli
New Direct-acting Antiviral Agents (DAA)-based anti-HCV therapies currently provide extraordinary opportunities to cure patients. Drug-drug interactions are however a real challenge during treatment. In particular, in HIV-infected patients in cART, DAA choice is limited by such interactions, which can result both in reduced efficacy and toxicity. We report the case of a HIV-infected patient on cART with atazanavir/ritonavir/abacavir/lamivudine, who presented kidney and biliary lithiasis, the latter treated with endoscopic retrograde cholangiopancreatography and endoscopic biliary sphincterotomy, after beginning anti-HCV treatment with daclatasvir/sofosbuvir/ribavirin...
February 2017: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/28286567/grazoprevir-elbasvir-combination-therapy-for-hcv-infection
#15
REVIEW
Anaïs Vallet-Pichard, Stanislas Pol
Interferon-free regimens combine different second-wave direct-acting antiviral agents (DAAs), which target the main viral proteins involved in the replication cycle of hepatitis C virus (HCV): NS3/4A protease inhibitors (simeprevir or paritaprevir boosted by ritonavir), NS5B nucleos(t)idic (sofosbuvir) and nonnucleos(t)idic (dasabuvir) polymerase inhibitors, NS5A replication complex inhibitors (daclatasvir, ledipasvir, elbasvir, velpatasvir). Combinations of two or three DAAs, given for 8-24 weeks reach sustained virology response (SVR) rates greater than 90% with good tolerance...
January 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28286560/prevalence-of-end-of-treatment-rna-positive-sustained-viral-response-in-hcv-patients-treated-with-sofosbuvir-combination-therapies
#16
Miguel Malespin, Tamara Benyashvili, Susan L Uprichard, Alan S Perelson, Harel Dahari, Scott J Cotler
BACKGROUND: Some chronic hepatitis C virus (HCV), genotype 1 infected patients treated with direct antiviral agents (DAAs) remain viremic at end of treatment (EOT+), yet go on to achieve sustained virological response 12 weeks after completion of therapy (SVR12). The incidence of EOT+/SVR in patients with genotype 1 and other genotypes, as well as whether such patients achieve SVR24 remain in question. The aims of this study were to evaluate the frequency and durability of EOT+/SVR12&24 and other response categories in HCV genotype 1, 2, or 3 infected patients treated with DAA in clinical practice...
January 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28281085/efficacy-and-safety-of-sofosbuvir-based-regimens-in-chronic-hepatitis-c-patients-on-dialysis
#17
Narendra S Choudhary, Amit Kumar, Vijay Bodh, Shyam Bihari Bansal, Reetesh Sharma, Manish Jain, Sanjiv Saigal, Neeraj Saraf
INTRODUCTION: Patients with end-stage renal disease (ESRD) have poor treatment tolerance and outcome to interferon-based regimens. Sofosbuvir-based regimens have improved treatment success in chronic hepatitis C. There is limited data in ESRD patients as sofosbuvir is excreted by the kidney. Several small studies have shown good results. METHODS: Sixteen consecutive patients of ESRD (on dialysis) and chronic hepatitis C were treated with sofosbuvir-based regimens as they were prospective kidney transplantation recipients, at a tertiary care center in north India...
March 9, 2017: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/28280374/optimizing-choice-of-oral-interferon-free-treatment-for-genotype-1-hepatitis-c-virus-using-testing-for-ns5a-resistance-a-cost-utility-analysis-from-the-perspective-of-the-italian-national-health-service
#18
Kirsten Y Westerhout, Walter Bouwmeester, Inge Duchesne, Marta Pisini, Marjanne A Piena, Francesco Damele, Beatrice Gueron, Maarten Treur, Jonathan Belsey
BACKGROUND: Patients with genotype-1 hepatitis C virus infection who have failed to respond to standard therapy or who relapse following treatment may be considered for an interferon-free regimen incorporating a nonstructural protein 5A (NS5A) inhibitor. Sustained virologic response (SVR) with these regimens is typically >90%, but this is reduced in patients with NS5A resistance. European Association for Study of the Liver guidelines recommend simeprevir + sofosbuvir ± ribavirin (SMV+SOF±R) for re-treating patients failing an NS5A inhibitor-containing regimen...
2017: ClinicoEconomics and Outcomes Research: CEOR
https://www.readbyqxmd.com/read/28277812/considerations-on-bringing-warehoused-hcv-patients-into-active-care-following-interferon-free-direct-acting-antiviral-drug-approval
#19
Aleksandra Palak, Christine Livoti, Céline Audibert
OBJECTIVES: Until recently, lack of efficacious and tolerable hepatitis C virus (HCV) treatments prompted patient warehousing until better treatment options became available. We investigated whether the introduction of ledipasvir/sofosbuvir precipitated patient return to clinics, thereby changing HCV clinic dynamics. METHODS: Online questionnaire responses indicated the volume of HCV patients followed, the proportion of warehoused patients and those who were proactively offered new options, methods for identifying and contacting patients, and insurance authorization/reimbursement-related information...
March 9, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28276815/effectiveness-of-interferon-free-therapy-for-the-treatment-of-hcv-patients-with-compensated-cirrhosis-treated-through-the-irish-early-access-program
#20
Emma Gray, Aisling O'Leary, Colm Bergin, Suzanne Norris
BACKGROUND: We investigated the real-world effectiveness of interferon-free regimens for the treatment of patients with compensated cirrhosis infected with hepatitis C virus (HCV). METHOD: Using the Irish national HCV treatment registry, the effectiveness and safety of interferon-free regimens for HCV-infected patients treated between April 2015 and August 2016, was determined. RESULTS: A SVR12 was achieved in 86% of subjects treated with sofosbuvir/ledipasvir ± ribavirin (SOF/LDV±RBV), 93% treated with paritaprevir, ombitasvir and ritonavir combined with dasabuvir ± ribavirin (3D±RBV) and 89% treated with sofosbuvir/daclatasvir ± ribavirin (SOF/DCV±RBV)...
February 22, 2017: Expert Review of Gastroenterology & Hepatology
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