Clinical Pharmacology of Maribavir (SHP620): A Comprehensive Overview

The Journal of Clinical Pharma

Chen

et al. 2022

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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 (C max ) 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, C max and AUC values for unbound maribavir were comparable. For VP 44469, the main metabolite of maribavir, the C max 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.

Section: Discussioncontrasting

confidence: 49%

Section: Discussionmentioning

confidence: 51%

Section: Discussionmentioning

confidence: 99%

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

The Journal of Clinical Pharma

Chen

et al. 2022

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“…was generally well-tolerated; taste disturbance (dysgeusia), nausea, and diarrhea were notable treatment-emergent adverse events (TEAEs) that seemed to be associated with maribavir. [19][20][21] Currently, maribavir at a dose of 400 mg b.i.d. is under investigation in two phase III studies for the treatment of transplant recipients with CMV infection, including resistant or refractory CMV and CMV disease (NCT02927067 and NCT02931539).…”

Section: How Might This Change Clinical Pharmacol-ogy or Translationamentioning

confidence: 99%

“…to 1,200 mg b.i.d. was generally well‐tolerated; taste disturbance (dysgeusia), nausea, and diarrhea were notable treatment‐emergent adverse events (TEAEs) that seemed to be associated with maribavir 19–21 . Currently, maribavir at a dose of 400 mg b.i.d.…”

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confidence: 99%

Evaluation of the Effect of Maribavir on Cardiac Repolarization in Healthy Participants: Thorough QT/QTc Study

Ilic

Clinical Translational Sci

et al. 2020

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Pharmacokinetics and Safety Evaluation of Maribavir in Healthy Japanese and Matched White Participants: A Phase 1, Open‐Label Study

Clinical Pharm in Drug Dev

Suttle²,

et al. 2023

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This phase I study compared pharmacokinetics and safety of maribavir in Japanese and White participants, and evaluated dose proportionality in Japanese participants. Under fasting conditions, 12 healthy adult participants of Japanese descent and 12 matched White participants received a single 400‐mg dose of maribavir. Japanese participants received 2 further doses of maribavir: 200 mg and 800 mg, or 800 mg and 200 mg, separated by a ≥72‐hour washout period. Serial blood samples were collected up to 24 hours after dosing for pharmacokinetic assessments. Following the 400‐mg dose, the geometric mean ratios (90% confidence interval) of Japanese versus White participants were 110% (91.7%–133%) for maximum plasma concentration, 122% (96.8%–155%) for area under the plasma concentration–time curve (AUC) from time of dosing to the last measurable concentration, and 125% (98.0%–160%) for AUC extrapolated to infinity. In Japanese participants, maribavir AUC extrapolated to infinity and AUC from time of dosing to the last measurable concentration increased in a dose‐proportional fashion over 200–800 mg; maximum plasma concentration increased less than dose proportionally. Seven participants reported treatment‐emergent adverse events (TEAEs; Japanese participants, 400 mg: 2 [16.7%], 200 mg: 1 [8.3%]; White participants, 400 mg: 4 [33.3%]), all mild and most commonly dysgeusia. No serious TEAEs or TEAEs leading to discontinuation were reported. This study demonstrated higher maribavir systemic exposure in Japanese than White participants and similar safety outcomes. This difference in exposure is not considered clinically important and its significance remains to be determined.