Maribavir Pharmacokinetics and Safety in Participants With Moderate Hepatic Impairment: A Phase 1, Open‐Label, Single‐Dose, Parallel Group Study

Maribavir, an orally bioavailable antiviral, has shown superior activity against posttransplant cytomegalovirus infection compared with conventional antivirals. It is primarily metabolized in the liver. This open‐label, single‐center study evaluated the effect of hepatic impairment on the pharmacoki...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2023-02, Vol.63 (2), p.250-258
Main Authors: Song, Ivy, Chen, Grace, Wu, Jingyang, Ilic, Katarina
Format: Article
Language:English
Subjects:
Adverse events
Antiviral agents
Area Under Curve
Benzimidazoles
CMV infection
Cytomegalovirus
hepatic impairment
Humans
Liver
Liver Diseases - metabolism
maribavir
Oral administration
Pharmacokinetics
pharmacokinetics and drug metabolism
Ribonucleosides
Special Populations
Taste disorders
transplantation
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Summary:Maribavir, an orally bioavailable antiviral, has shown superior activity against posttransplant cytomegalovirus infection compared with conventional antivirals. It is primarily metabolized in the liver. This open‐label, single‐center study evaluated the effect of hepatic impairment on the pharmacokinetics of maribavir in nontransplant participants. A single 200‐mg dose of maribavir was administered orally under fasting conditions to participants with moderate hepatic impairment (Child–Pugh class B) (n = 10) and healthy controls (n = 10) matched for age, weight, sex, and smoking status. Compared with participants with normal hepatic function, maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) from time 0 to infinity values for maribavir in participants with moderate hepatic impairment were 1.346‐fold (90%CI of geometric mean ratio, 1.091–1.660) and 1.261‐fold (0.889–1.787) higher, respectively. However, Cmax and AUC values for unbound maribavir were comparable. For VP 44469, the main metabolite of maribavir, the Cmax and AUC from time 0 to infinity values were 1.190‐fold (0.836–1.693) and 1.309‐fold (1.007–1.702) higher, respectively, in participants with moderate hepatic impairment. In total, 7 mild treatment‐emergent adverse events were reported, all in the moderate hepatic impairment group. Dysgeusia was the most frequently reported treatment‐emergent adverse event, at a frequency of 50%. These results indicated that total maribavir concentrations were mildly increased in participants with moderate hepatic impairment, while unbound concentrations were unaffected. Similar maribavir pharmacokinetics in participants with moderate hepatic impairment and normal hepatic function suggest that dose adjustment may not be required for patients with moderate hepatic impairment.
ISSN:0091-2700
1552-4604
DOI:10.1002/jcph.2155