The Journal of antimicrobial chemotherapy · 2026
Monte Carlo simulations identify suboptimal PK/PD target attainment with standard maribavir dosing.
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Fromage Yeleen, Sayadi Hamza, Labriffe Marc, Codde Cyrielle, Alain Sophie, Marquet Pierre, Woillard Jean-Baptiste, Monchaud Caroline
Аннотация
BACKGROUND: Maribavir is currently administered at a dose of 400 mg twice daily (q12h) for the treatment of cytomegalovirus (CMV) infections in transplant recipients. However, virological failure rates of up to 40% have been reported in clinical practice, with potentially severe consequences and the selection of mutant strains.
OBJECTIVES: This study aims to evaluate, in silico, the pharmacokinetic (PK) and pharmacodynamic (PD) interest of alternative maribavir dosing regimens using population pharmacokinetic (POPPK) modelling and Monte Carlo simulations.
METHODS: A published two-compartment POPPK model with first-order absorption and an absorption lag time was implemented. Monte Carlo simulations (n = 10 000 virtual PK profiles) were performed for maribavir regimens of 400, 600, and 800 mg administered q12h and every 8 h (q8h). PK metrics, including trough concentration (C0) and area under the concentration-time curve (AUC), as well as probability of target attainment (PTA), were compared across regimens at steady state.
RESULTS: The standard 400 mg q12h regimen resulted in the lowest PTA, falling below 90% for a pharmacologically active inhibitory concentration 50 of 2 mg/L. In contrast, q8h regimens substantially improved PTA across targets and were associated with reduced interindividual variability in C0.
CONCLUSIONS: Increasing dosing frequency to a three-times-daily regimen improved PK/PD target attainment compared with the standard q12h regimen. These findings support the need for prospective clinical and pharmacoeconomic studies to assess the benefit-risk balance of alternative maribavir dosing strategies.
OBJECTIVES: This study aims to evaluate, in silico, the pharmacokinetic (PK) and pharmacodynamic (PD) interest of alternative maribavir dosing regimens using population pharmacokinetic (POPPK) modelling and Monte Carlo simulations.
METHODS: A published two-compartment POPPK model with first-order absorption and an absorption lag time was implemented. Monte Carlo simulations (n = 10 000 virtual PK profiles) were performed for maribavir regimens of 400, 600, and 800 mg administered q12h and every 8 h (q8h). PK metrics, including trough concentration (C0) and area under the concentration-time curve (AUC), as well as probability of target attainment (PTA), were compared across regimens at steady state.
RESULTS: The standard 400 mg q12h regimen resulted in the lowest PTA, falling below 90% for a pharmacologically active inhibitory concentration 50 of 2 mg/L. In contrast, q8h regimens substantially improved PTA across targets and were associated with reduced interindividual variability in C0.
CONCLUSIONS: Increasing dosing frequency to a three-times-daily regimen improved PK/PD target attainment compared with the standard q12h regimen. These findings support the need for prospective clinical and pharmacoeconomic studies to assess the benefit-risk balance of alternative maribavir dosing strategies.