Effects of Maribavir on P-Glycoprotein and CYP2D6 in Healthy Volunteers.

Journal of Clinical Pharmacology
Ivy H SongPatrick Martin

Abstract

Maribavir is an investigational drug being evaluated in transplant recipients with cytomegalovirus infection. To understand potential drug-drug interactions, we examined the effects of multiple doses of maribavir on cytochrome P450 (CYP) 2D6 and P-glycoprotein (P-gp) activity using probe substrates in healthy volunteers. During this phase 1 open-label study (NCT02775240), participants received the probe substrates digoxin (0.5 mg) and dextromethorphan (30 mg) before and after maribavir (400 mg twice daily for 8 days). Serial plasma samples were analyzed for digoxin, dextromethorpha, dextrorphan, and maribavir concentrations. Pharmacokinetic parameters were calculated (noncompartmental analysis) and analyzed with a linear mixed-effects model for treatment comparison to estimate geometric mean ratios (GMRs) and 90% confidence intervals (CIs). CYP2D6 polymorphisms were genotyped using polymerase chain reaction. Overall, 17 of 18 participants (94.4%) completed the study. All participants were genotyped as CYP2D6 intermediate/extensive metabolizers. GMR (90%CI) of digoxin Cmax , AUClast , and AUC0-∞ with and without maribavir was 1.257 (1.139-1.387), 1.187 (1.088-1.296), and 1.217 (1.110-1.335), respectively, outside the "no-effect"...Continue Reading

Associated Clinical Trials

References

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Jul 2, 2018·Drugs·Atibordee Meesing, Raymund R Razonable

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Citations

Jan 26, 2020·Current Hematologic Malignancy Reports·Morgan Hakki

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Methods Mentioned

BETA
Genotyping

Clinical Trials Mentioned

NCT02927067
NCT02931539

Software Mentioned

nQuery
SAS
Integreview

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