Contribution of Adsorption and Hematocrit Levels to Ganciclovir Clearance in an in Vitro Continuous Hemodiafiltration Model

Abstract

Estimation of the continuous hemodiafiltration (CHDF) clearance (CL_CHDF) of ganciclovir (GCV) is crucial for achieving efficient treatment outcomes. Here, we aimed to clarify the contribution of diafiltration, adsorption, and hematocrit level to the CL_CHDF of GCV in an in vitro CHDF model using three membranes: polyacrylonitrile and sodium methallyl sulfonate copolymer coated with polyethylenimine (AN69ST); polymethylmethacrylate (PMMA); and polysulfone (PS). In vitro CHDF was performed with effluent flow rates (Qe) of 800, 1500, and 3000 mL/h. The initial GCV concentration was 10 µg/mL while that of human serum albumin (HSA) was 0 or 5 g/dL. The CL_CHDF, diafiltration rates, and adsorption rates were calculated. The whole blood-to-plasma ratio (R) of GCV for a hematocrit of 0.1 to 0.5 was determined using blood samples with 0.5 to 100 µg/mL of GCV. The in vitro CHDF experiment using AN69ST, PMMA, and PS membranes showed that the total CL_CHDF values were almost the same as the Qe and not influenced by the HSA concentration. The diafiltration rate exceeded 88.1 ± 2.8% while the adsorption rate was lower than 9.4 ± 9.4% in all conditions. The R value was 1.89 ± 0.11 and was similar at all hematocrit levels and GCV concentrations. In conclusion, diafiltration mainly contributes to the CL_CHDF of GCV, rather than adsorption. Hematocrit levels might not affect the relationship between the plasma and blood CL_CHDF of GCV, and the CL_CHDF of GCV can be estimated from the Qe and R, at least in vitro.