letermovir and Liver-Diseases

Human cytomegalovirus constitutes a prevalent and serious threat to immunocompromised individuals and requires new treatments. Letermovir is a novel viral-terminase inhibitor that has demonstrated prophylactic/pre-emptive activity against human cytomegalovirus in Phase 2 and 3 transplant trials. As unchanged letermovir is primarily excreted via the liver by bile, this trial aimed to assess the effect of hepatic impairment on letermovir pharmacokinetics.. Phase 1, open-label, parallel-group pharmacokinetic and safety comparison of multiple once-daily oral letermovir in female subjects with hepatic impairment and healthy matched controls. For 8 days, subjects with moderate hepatic impairment (n = 8) and their matched healthy controls (n = 9) received 60 mg letermovir/day and those with severe hepatic impairment (n = 8) and their matched healthy controls (n = 8) received 30 mg letermovir/day. Pharmacokinetic parameters were determined from blood samples.. For subjects with moderate hepatic impairment, maximal observed concentration at steady state (C. Moderate hepatic impairment increased exposure to letermovir <2-fold, while severe hepatic impairment increased letermovir exposure approximately 4-fold as compared with healthy subjects. Letermovir 60/30 mg/day was generally well-tolerated in subjects with hepatic impairment.

Topics: Acetates; Administration, Oral; Adolescent; Adult; Aged; Antiviral Agents; Area Under Curve; Cytomegalovirus Infections; Drug Administration Schedule; Female; Half-Life; Humans; Liver; Liver Diseases; Metabolic Clearance Rate; Middle Aged; Quinazolines; Russia; Severity of Illness Index; Treatment Outcome; Young Adult

Topics: Acetates; Antiviral Agents; Child; Cytomegalovirus Infections; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Liver Diseases; Quinazolines; Transplant Recipients