SARS-CoV-2 viral dynamics in a placebo-controlled phase 2 study of patients infected with the SARS-CoV-2 Omicron variant and treated with pomotrelvir.

Current guidelines recommend that individuals with moderate COVID-19 disease isolate for 5 days after the first appearance of symptoms or a positive SARS-CoV-2 test. It would be useful to understand the time course of infectious virus production and its correlation with virus detection using a rapid antigen test (RAT) or quantitative reverse transcriptase (qRT)-PCR. In a phase 2 study, 242 vaccinated patients with COVID-19 and at low risk for progression to severe disease initiated 5 days of treatment with pomotrelvir (PBI-0451, a SARS-CoV-2 main protease inhibitor) or placebo within 5 days after symptom onset.

Characterization of Pharmacokinetics, Biotransformation and Elimination of Pomotrelvir Orally Administered in Healthy Male Adults Using Two [C]-Labeled Microtracers with Separate Labeling Positions.

Pomotrelvir is an orally bioavailable, target antiviral inhibitor of the main protease (M) of coronaviruses, including severe acute respiratory syndrome coronavirus 2, the etiological agent of Coronavirus Disease 2019. The pharmacokinetics, metabolism and elimination of two [C]-labeled microtracers of 5 Ci/700 mg pomotrelvir with separate labeling positions (isotopomers), [lactam carbonyl-C-pomotelvir] and [benzene ring-U-C-pomotrelvir], following a single oral dose in healthy adult males was evaluated in two separate cohorts. Pomotrelvir was rapidly absorbed and eliminated primarily through metabolism and subsequently excreted via urine and feces.

A comprehensive evaluation in clinic and physiologically-based pharmacokinetic modeling and simulation to confirm lack of cytochrome P450-mediated drug-drug interaction potential for pomotrelvir.

Pomotrelvir is a new chemical entity and potent direct-acting antiviral inhibitor of the main protease of coronaviruses. Here the cytochrome P450 (CYP)-mediated drug-drug interaction (DDI) potential of pomotrelvir was evaluated for major CYP isoforms, starting with in vitro assays followed by the basic static model assessment. The identified CYP3A4-mediated potential DDIs were evaluated clinically at a supratherapeutic dose of 1050 mg twice daily (b.

Resolution of organ dysfunction as a predictor of long-term survival in necrotizing soft tissue infections: Analysis of the AB103 Clinical Composite Endpoint Study in Necrotizing Soft Tissue Infections trial and a retrospective claims database-linked chart study.

Background: Necrotizing soft tissue infections (NSTIs) are an acute surgical condition with high morbidity and mortality. Timely identification, resuscitation, and aggressive surgical management have significantly decreased inpatient mortality. However, reduced inpatient mortality has shifted the burden of disease to long-term mortality associated with persistent organ dysfunction.

Estimating the Impact of Necrotizing Soft Tissue Infections in the United States: Incidence and Re-Admissions.

Previous estimates of the incidence of necrotizing soft tissue infections (NSTI) in the United States have substantial limitations and underestimate its occurrence. Improvements in hospital mortality after NSTI have increased the number of survivors at risk for long-term sequelae. This study estimates the incidence of NSTI and the burden of re-admission and associated healthcare spending in patients who survived admission for NSTI.