ritonavir

Momelotinib-approved for treatment of myelofibrosis in adults with anemia-and its major active metabolite, M21, were assessed as drug-drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple-dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single-dose rifampin), and a strong CYP3A4 inducer (multiple-dose rifampin). Momelotinib DDI perpetrator potential (multiple-dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respectively)...

After a downward trend for more than 12 months, the incidence of COVID-19 has increased in the last months. Although COVID-19 is not as frequent as in the first years of the pandemic, case numbers are still very high, and it causes a significant number of deaths. COVID-19 is not seen with a predictable frequency, at least two times more deadly than the flu, continues as an epidemic, and has not reached the endemic level yet. Currently, the Omicron strains EG.5 and XBB.1.16 are dominant worldwide. Although BA...

JC polyomavirus (JCPyV) is a human polyomavirus that can establish lifelong persistent infection in the majority of adults. It is typically asymptomatic in immunocompetent individuals. However, there is a risk of developing progressive multifocal leukoencephalopathy (PML) in immunocompromised or immunosuppressed patients. Though JCPyV commonly resides in the kidney-urinary tract, its involvement in urinary system diseases is extremely rare. Here, we reported a case of a 60-year-old male patient with coronavirus disease 2019 (COVID-19) infection who developed hemorrhagic cystitis after receiving treatment with nirmatrelvir 300 mg/ritonavir 100 mg quaque die (QD)...

OBJECTIVES: This study was conducted to assess the efficacy of nirmatrelvir/ritonavir treatment in patients with coronavirus disease 2019 (COVID-19), particularly those aged 60 years and older. Using real-world data, the period during which the BN.1 Omicron variant was dominant was compared to the period dominated by the BA.5 variant. METHODS: In this retrospective cohort study, data were collected regarding 2,665,281 patients infected with severe acute respiratory syndrome coronavirus 2 between July 24, 2022, and March 31, 2023...

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (Mpro ) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug...

OBJECTIVE: The efficacy of nirmatrelvir-ritonavir for hospitalized patients with COVID-19 has not been fully established. METHODS: We conducted a retrospective analysis of hospitalized COVID-19 patients with high risk for disease progression at Beijing Chaoyang Hospital from October 15, 2022, to March 31, 2023. Patients ≥18 years old who were hospitalized with COVID-19 within 5 days of symptom onset were included. Baseline data were obtained from the routine electronic health record database of the hospital information system...

BACKGROUND: GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C like protease inhibitor that has demonstrated greater potency and efficacy compared to Nirmatrelvir in pre-clinical studies. We aimed to evaluate the efficacy and safety of orally administered GST-HG171 plus Ritonavir in patients with coronavirus disease 2019 (COVID-19) infected with emerging XBB and non-XBB variants. METHODS: This randomised, double-blind, placebo-controlled phase 2/3 trial was conducted in 47 sites in China among adult patients with mild-to-moderate COVID-19 with symptoms onset ≤72 h...

We aimed to address factors contributing to the pharmacokinetic changes of nirmatrelvir/ritonavir in renal impaired (RI) patients and recommend dosing adjustment via a physiologically-based pharmacokinetic (PBPK) modelling approach. A PBPK model of nirmatrelvir/ritonavir was developed via Simcyp® Simulator. Sensitivity analysis of the influence of hepatic CYP3A4 intrinsic clearance and abundance, as well as hepatic non-CYP3A4 metabolism (other human liver microsomes [HLM] CLint ) was performed to evaluate the effects of RI on oral clearance of nirmatrelvir...

It is desirable to predict positive food effect of oral formulations due to food mediated dissolution enhancement of lipophilic drugs. The objective was to assess the ability of in vitro lipolysis to anticipate a positive food effect. Tested formulations included rivaroxaban and itraconazole, where some formulations, but not all, exhibit a positive food effect in vivo in humans. Amorphous solid dispersion formulations of ritonavir, which exhibit a negative food effect in vivo in humans, were also studied. Fe-lipolysis and Fa-lipolysis media representing fed and fasted intestinal conditions were used...

Ritonavir is a potent inhibitor of the cytochrome P450 3A4 enzyme and is commonly used as a pharmacokinetic (PK) enhancer in antiviral therapies because it increases bioavailability of concomitantly administered antivirals. Decades of experience with ritonavir-enhanced HIV therapies and, more recently, COVID-19 therapies demonstrate that boosting doses of ritonavir are well tolerated, with an established safety profile. The mechanisms of PK enhancement by ritonavir result in the potential for drug-drug interactions (DDIs) with several classes of drugs, thus making co-medication management an important consideration with enhanced antiviral therapies...

PURPOSE: To evaluate clinical outcomes associated with sotrovimab use during Omicron BA.2 and BA.5 predominance. METHODS: Electronic databases were searched for observational studies published in peer-reviewed journals, preprint articles and conference abstracts from January 1, 2022 to February 27, 2023. RESULTS: The 14 studies identified were heterogeneous in terms of study design, population, endpoints and definitions. They included > 1...

Patients with systemic autoimmune rheumatic diseases are at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and effective antiviral treatments including nirmatrelvir/ritonavir can improve their outcomes. However, there might be potential drug-drug interactions when these patients take nirmatrelvir/ritonavir together with immunosuppressants with a narrow therapeutic window, such as tacrolimus and cyclosporine. We present a case of paralytic ileus resulting from tacrolimus toxicity mediated by the use of nirmatrelvir/ritonavir in a patient with systemic lupus erythematosus (SLE)...

BACKGROUND: In China, both nirmatrelvir-ritonavir (Paxlovid) and azvudine have been granted approval to treat adult SARS-CoV-2-infected patients with moderate symptoms. Information about the clinical effect of the two available agents among inpatients with severe or critical COVID-19 is scarce. PURPOSE: To compare the clinical outcomes of Paxlovid and azvudine among adult inpatients with severe or critical COVID-19. METHOD: We conducted a retrospective cohort study in two large medical centres after the epidemic control measures were lifted in China...

AIM: This study aims to design chemically crosslinked thiolated cyclodextrin-based hydrogels and to evaluate their mucoadhesive properties via mucosal residence time studies on porcine small intestinal mucosa and on porcine buccal mucosa. METHODS: Free thiol groups of heptakis(6-deoxy-6-thio)-β-cyclodextrin (β-CD-SH) were S-protected with 2-mercaptoethanesulfonic acid (MESNA) followed by crosslinking with citric acid. Cytotoxicity was assessed by hemolysis as well as resazurin assay...

BACKGROUND: Nirmatrelvir in combination with ritonavir is an antiviral treatment for mild-to-moderate coronavirus disease 2019 (Covid-19). The efficacy of this treatment in patients who are at standard risk for severe Covid-19 or who are fully vaccinated and have at least one risk factor for severe Covid-19 has not been established. METHODS: In this phase 2-3 trial, we randomly assigned adults who had confirmed Covid-19 with symptom onset within the past 5 days in a 1:1 ratio to receive nirmatrelvir-ritonavir or placebo every 12 hours for 5 days...

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context...

In recent years, the application of fixed dose combinations of antiretroviral drugs in HIV therapy has been established. Despite numerous therapeutic benefits, this approach poses several challenges for the formulation development especially when poorly soluble drugs are considered. Amorphous solid dispersions (ASD) thereby have gained considerable interest in the pharmaceutical field, however, mainly including binary systems containing only one drug and a polymer. The co -formulation of two amorphous drugs can be accompanied by an immense increase in the complexity of the system as exemplarily reported for ritonavir and lopinavir embedded in a composite polymer matrix of PVPVA...

The main protease (Mpro ) of SARS-CoV-2 is critical in the virus's replication cycle, facilitating the maturation of polyproteins into functional units. Due to its conservation across taxa, Mpro is a promising target for broad-spectrum antiviral drugs. Targeting Mpro with small molecule inhibitors, such as nirmatrelvir combined with ritonavir (Paxlovid™), which the FDA has approved for post-exposure treatment and prophylaxis, can effectively interrupt the replication process of the virus. A key aspect of Mpro 's function is its ability to form a functional dimer...

BACKGROUND: Since coronavirus 2019 (COVID-19) swept the world, a variety of novel therapeutic and prevention strategies have been developed, among which nirmatrelvir-ritonavir is highly recommended. We intended to assess the effectiveness and safety of nirmatrelvir-ritonavir in the elderly mild-to-moderate COVID-19 population caused by the omicron BA.2.2 variant in real-world settings. METHODS: An observational study was conducted retrospectively to review the outcomes of mild-to-moderate COVID-19 patients admitted between April 26 and June 30, 2022...

OBJECTIVES: This study investigated the association between nirmatrelvir plus ritonavir (NMV-r) or molnupiravir and the outcomes of non-hospitalized high-risk patients with COVID-19 during Omicron XBB subvariants. METHODS: The retrospective cohort study used the TriNetX US collaborative network to identify non-hospitalized high-risk adult patients with COVID-19 between 1 February 2023, and 31 August 2023. Propensity score matching (PSM) was used to match patients receiving NMV-r or MOV (the study group) with those not receiving antivirals (the control group)...