Human bronchopulmonary disposition and plasma pharmacokinetics of oral bemnifosbuvir (AT-527), an experimental guanosine nucleotide prodrug for COVID-19.

Background: Bemnifosbuvir (AT-527) is a novel oral guanosine nucleotide antiviral drug for the treatment of persons with COVID-19. Direct assessment of drug disposition in the lungs, via bronchoalveolar lavage, is necessary to ensure antiviral drug levels at the primary site of SARS-CoV-2 infection are achieved.

Objectives: This Phase 1 study in healthy subjects aimed to assess the bronchopulmonary pharmacokinetics, safety and tolerability of repeated doses of bemnifosbuvir.

First-in-human trial evaluating safety and pharmacokinetics of AT-752, a novel nucleotide prodrug with pan-serotype activity against dengue virus.

AT-752 is a novel guanosine nucleotide prodrug inhibitor of the dengue virus (DENV) polymerase with sub-micromolar, pan-serotype antiviral activity. This phase 1, double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of ascending single and multiple oral doses of AT-752 in healthy subjects. AT-752 was well tolerated when administered as a single dose up to 1,500 mg or when administered as multiple doses up to 750 mg three times daily (TID).

Bemnifosbuvir (BEM, AT-527), a novel nucleotide analogue inhibitor of the hepatitis C virus NS5B polymerase.

Introduction: Chronic hepatitis C virus (HCV) persists as a public health concern worldwide. Consequently, optimizing HCV therapy remains an important objective. While current therapies are generally highly effective, advanced antiviral agents are needed to maximize cure rates with potentially shorter treatment durations in a broader patient population, particularly those patients with advanced diseases who remain difficult to treat.

Phase II study of bemnifosbuvir in high-risk participants in a hospital setting with moderate COVID-19.

Background: Bemnifosbuvir, a novel, oral, nonmutagenic, nonteratogenic nucleotide analogue inhibits SARS-CoV-2 replication .

Materials & Methods: Adults in hospital settings with moderate COVID-19 were randomized 1:1 bemnifosbuvir/placebo. Study amended to two parts after interim analysis; part B enrollment limited owing to evolving standard of care.

Oral bemnifosbuvir (AT-527) vs placebo in patients with mild-to-moderate COVID-19 in an outpatient setting (MORNINGSKY).

This phase III study assessed the efficacy/safety/antiviral activity/pharmacokinetics of bemnifosbuvir, a novel, oral nucleotide analog to treat COVID-19. Outpatient adults/adolescents with mild-to-moderate COVID-19 were randomized 2:1 to bemnifosbuvir/placebo. Time to symptom alleviation/improvement (primary outcome), risk of hospitalization/death, viral load and safety were evaluated.

Interferon-free regimens containing setrobuvir for patients with genotype 1 chronic hepatitis C: a randomized, multicenter study.

Background & Aims: Setrobuvir is a direct-acting antiviral (DAA) non-nucleoside inhibitor of hepatitis C virus (HCV) polymerase. This study examined interferon-free combinations containing setrobuvir, a ritonavir-boosted protease inhibitor (danoprevir/r) and ribavirin, with/without the nucleoside inhibitor mericitabine in HCV genotype (G)1 patients.

Methods: Non-cirrhotic treatment-naïve patients (N = 110) were randomized to five groups.

Mericitabine and ritonavir-boosted danoprevir with or without ribavirin in treatment-naive HCV genotype 1 patients: INFORM-SVR study.

Background & Aims: Safety and tolerability of peginterferon-based hepatitis C virus (HCV) infection therapy remains suboptimal, even when direct-acting antiviral agents are added. This study assessed the efficacy, safety and tolerability of mericitabine combined with ritonavir-boosted danoprevir (danoprevir/r) ± ribavirin for up to 24 weeks in treatment-naïve HCV genotype (G)1 infected patients.

Methods: Patients received twice daily mericitabine (1000 mg) and danoprevir/r (100 mg/100 mg) plus either ribavirin (1000/1200 mg/day; Arm A) or placebo (Arm B) for 12 or 24 weeks.

A randomized, double-blind placebo controlled trial of balapiravir, a polymerase inhibitor, in adult dengue patients.

Background: Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of hepatitis C virus replication in vivo.

The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels.

Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; North American adopted name), a first-in-class antiepileptic drug (AED) that reduces neuronal excitability primarily by enhancing the activity of KCNQ2/3 (K(v)7.2/7.3) potassium channels, has recently been approved by the European Medicines Agency and the U.

Virologic response rates of weight-based taribavirin versus ribavirin in treatment-naive patients with genotype 1 chronic hepatitis C.

Unlabelled: Ribavirin-induced hemolytic anemia can prompt dose reductions and lower sustained virologic response (SVR) rates in the treatment of patients with chronic hepatitis C. The study aimed to determine if weight-based dosing of taribavirin (TBV), an oral prodrug of ribavirin (RBV), demonstrated efficacy comparable to RBV while maintaining its previously demonstrated anemia advantage with fixed dose administration. A U.

Molecular ions and protonated molecules observed in the atmospheric solids analysis probe analysis of steroids.

Atmospheric pressure chemical ionisation (APCI) has often been used to ionise steroids in mass spectrometry, usually when interfaced to high-performance liquid chromatography (HPLC). However, in positive ion mode, a dehydrated protonated molecule is often observed with a loss of structural information. The recently introduced technique of atmospheric solids analysis probe (ASAP) has the advantage that the sample can be analysed directly and does not need to be interfaced to HPLC.

Efficacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy regimens in antiretroviral-naive patients.

Background: Atazanavir (ATV), the first once-daily protease inhibitor approved for the treatment of HIV-1 infection, is recommended for use in antiretroviral (ARV) treatment-naive and -experienced patients. Study AI424-089 was a prospective, randomized, open-label, 96-week study comparing 2 ATV-based treatment regimens in ARV-naive HIV-infected patients.

Methods: Adults with HIV RNA levels > or =2000 copies/mL were randomized (1:1) to once-daily ATV at a dose of 300 mg with ritonavir at a dose of 100 mg (ATV300/RTV) or ATV at a dose of 400 mg (ATV400); both regimens included lamivudine and an investigational extended-release formulation of stavudine.

Inhaled zanamivir versus rimantadine for the control of influenza in a highly vaccinated long-term care population.

Background: Despite vaccination, influenza commonly causes morbidity and mortality in institutional settings. Influenza control with rimantadine and amantadine is limited by emergence and transmission of drug-resistant influenza A variants, ineffectiveness against influenza B, and toxicity. This study evaluated the efficacy and tolerability of zanamivir versus rimantadine for influenza outbreak control in long-term care facilities.

Vancomycin-sensitive and vancomycin-resistant enterococcal infections in the ICU: attributable costs and outcomes.

Objectives: To determine the economic and clinical outcomes associated with infection with vancomycin-resistant Enterococcus (VRE) and to compare these outcomes to those associated with infection with vancomycin-sensitive Enterococcus (VSE).

Methods: During a 3-month, prospective, cohort study of 117 high-risk, critically ill patients we collected complete clinical and demographic and ICU cost data from all patients during their ICU stays.

Results: After adjusting for variables in a stepwise multiple regression model VRE infections were associated with a median attributable increased ICU cost per patient of $33,251 (38,088 euros) and an increased length of hospital stay (LOS) of 22 days, while VSE infections were associated with an increased cost of $21,914 (25,102 euros) and an increased LOS of 27 days.