Monte Carlo simulations identify suboptimal PK/PD target attainment with standard maribavir dosing.

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.