Contribution of Adsorption and Hematocrit Levels to Ganciclovir Clearance in an <i>in Vitro</i> 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.