Maribavir pharmacokinetics during in vitro continuous renal replacement therapy

Maribavir is a well-tolerated option for drug-resistant CMV, though there is no available guidance for dosing in patients on continuous renal replacement therapy (CRRT). This study aimed to determine maribavir clearance and hemofilter adsorption during CRRT to inform dosing recommendations. Maribavir pharmacokinetic profiles were quantified using an in vitro model. Total clearance during CRRT (CLCRRT) in addition to sieving (SC), and saturation (SA) coefficients were calculated based on these experiments. Optimal maribavir doses were then estimated from the in vitro parameters. The mean SA was 0.853 and did not differ by filter type ( P = 0.831). The SC was higher with the M150 filter (0.102) than for the HF1400 filter (0.080; P = 0.040). Across all experiments, the mean maribavir CLCRRT ranged from 0.19 to 0.49 L/hr and did not significantly differ between continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) ( P = 0.853) but was higher at 4 vs. 2 L/hr ( P = 0.007). The mean CLCRRT was lower with the M150 filter compared to the HF1400 filter ( P = 0.063), which was attributed to the higher adsorption with HF1400. Filter type and effluent flow rate were independently associated with CLCRRT for CVVH whereas only effluent flow rate was independently associated with CLCRRT for CVVHD. The package insert dose of 400 mg twice daily would lead to adequate concentrations across the most common flow rates (1–4 L/hr) with either modality or filter type. Maribavir clearance during CRRT was relatively low, though it adsorbed significantly more to the HF1400 filter. At typical CRRT flow rates, standard dosing of 400 mg twice daily is predicted to provide adequate exposures.