Leritrelvir

This study evaluated the safety and pharmacokinetics (PK) of a single dose of leritrelvir, a novel inhibitor of 3-chymotrypsin-like cysteine protease (3CLpro), in patients with hepatic impairment versus healthy participants with normal hepatic function. Eight participants with mild (Child–Pugh A) hepatic impairment, eight with moderate (Child–Pugh B) hepatic impairment, and eight healthy matched control participants were enrolled in this open-label, parallel clinical trial. After administration of leritrelvir of 400 mg, PK parameters were calculated and compared across groups. In total, 24 participants were enrolled and completed the study. Leritrelvir was generally well tolerated, with no serious adverse events or deaths reported during the study. Compared to the group with normal hepatic function, the geometric least-squares mean ratios (90% confidence intervals) for Cmax , AUC 0- t , and AUC 0-∞ of leritrelvir in participants with mild hepatic impairment were 96.9% (69.3%, 135%), 92.2% (69.6%, 122%), and 92.1% (69.7%, 122%), respectively. For moderate hepatic impairment, the corresponding ratios were 91.6% (61.7%, 136%), 113% (80.0%, 160%), and 113% (80.0%, 159%). Leritrelvir exposures were comparable among the three groups. Overall, there was no clinically relevant difference in leritrelvir exposure in participants with hepatic impairment compared to normal controls. No dose adjustment is required for leritrelvir in patients with mild or moderate hepatic impairment.

This study is registered with ClinicalTrials.gov as NCT06161259 .

SARS-CoV-2 has undergone five major transformations from its original strain, evolving through Alpha, Beta, Gamma, Delta, and now Omicron.The Omicron variant stands out for its high transmissibility, reduced severity, mild symptoms, and low mortality.Today, Omicron infections have become akin to common upper respiratory tract infections, underscoring the critical role of oral therapeutic drugs in clin. settings.These small-mol. oral antivirals are game-changers, effectively preventing mild and moderate cases from escalating to severe conditions and significantly reducing mortality among severe cases.They have emerged as the frontline defenders in the fight against SARS-CoV-2.Currently, eight oral antiviral drugs have been approved for use, including four 3CL protease inhibitors (nirmatrelvir/ritonavir, simnotrelvir/ritonavir, atilotrelvir/ritonavir, ensitrelvir, and leritrelvir), and three RNA polymerase inhibitors (molnupiravir, azvudine, and deuterium remdesivir).These medications are readily available and have ensured an uninterrupted clin. supply.With the establishment of a robust post-infection immune barrier and the widespread clin. use of oral antiviral drugs, the global threat posed by the COVID-19 pandemic has significantly diminished.The relentless march of scientific progress and medical innovation has turned the tide, making COVID-19 a manageable part of our lives.