Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Maribavir, an investigational agent for cytomegalovirus (CMV) infection in transplant recipients, has received Breakthrough Therapy Designation. Maribavir is metabolized primarily in the liver through cytochrome P450 (CYP) 3A4 (primary) and CYP1A2 (secondary); renal clearance is a minor route (<5%). The pharmacokinetics (PK) of maribavir in adult subjects with moderate hepatic impairment was compared to subjects with normal hepatic function.
*Methods: This Phase 1, open-label study enrolled 10 subjects with moderate hepatic impairment (Child-Pugh Class B) and 10 subjects with normal hepatic function of similar age, weight, sex, and smoking status. A single 200 mg dose of maribavir was administered under fasting conditions. Blood samples were collected for PK evaluation before and through 48 hours after study drug administration. PK parameters were compared between the two groups using ANOVA. Safety evaluations included physical examination, adverse events (AE), vital signs, 12-lead ECGs, and clinical laboratory tests.
*Results: All 20 subjects (70% female) completed the study. Subjects with moderate hepatic impairment had higher maximum total plasma maribavir concentrations (Cmax) (by about 35%) and area under the curve (AUC) values (by about 25%) than normal subjects. However, Cmax and AUC values of unbound maribavir concentrations in plasma for the two groups were comparable. The variability of unbound AUC values was greater for subjects with hepatic impairment (coefficient of variation [CV], 55%) than for normal subjects (CV, 28%). For VP 44469 (the major metabolite of maribavir in plasma) PK, subjects with moderate hepatic impairment tended to show slightly longer half-life and lower clearance (ie, higher AUC values) than normal subjects. A single oral dose of maribavir 200 mg was well tolerated by both groups. Treatment-emergent AEs were experienced by 70% of subjects with moderate hepatic impairment. Mild dysgeusia was the only AE reported for more than one subject and was reported in 50% of subjects. No subjects with normal hepatic function reported an AE.
*Conclusions: Given the wide therapeutic index of maribavir, maribavir dose adjustment in patients with mild-to-moderate hepatic impairment is not required.
To cite this abstract in AMA style:Song IH, Ilic K, Wu J. Pharmacokinetics of Maribavir in Subjects with Moderate Hepatic Impairment [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/pharmacokinetics-of-maribavir-in-subjects-with-moderate-hepatic-impairment/. Accessed May 8, 2021.
« Back to 2020 American Transplant Congress