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Published on: May 10, 2013
Contribution of Adsorption and Hematocrit Levels to Ganciclovir Clearance in an in Vitro Continuous Hemodiafiltration
Yanika Roongpairoj1, Masashi Uchida2, Shingo Yamazaki1,2
1Graduate School of Pharmaceutical Sciences, Chiba University.
Insights
Diafiltration, not adsorption, is the primary driver of ganciclovir clearance during continuous hemodiafiltration (CHDF). Ganciclovir clearance in CHDF can be estimated using effluent flow rate and the blood-to-plasma ratio, independent of hematocrit.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Nephrology and Critical Care
- Biomaterials Science
Background:
- Accurate estimation of ganciclovir clearance (CLCHDF) is vital for effective continuous hemodiafiltration (CHDF) treatment.
- Understanding the factors influencing CLCHDF, such as membrane type and hematocrit, is crucial for optimizing antiviral therapy in critically ill patients.
Purpose of the Study:
- To investigate the contributions of diafiltration and adsorption to ganciclovir's CLCHDF using three distinct dialysis membranes.
- To determine the impact of hematocrit levels on the whole blood-to-plasma ratio (R) of ganciclovir.
Main Methods:
- In vitro CHDF experiments were conducted using AN69ST, PMMA, and PS membranes at varying effluent flow rates (Qe).
- Ganciclovir and human serum albumin concentrations were monitored, and diafiltration and adsorption rates were calculated.
- The whole blood-to-plasma ratio (R) of ganciclovir was determined across a range of hematocrit levels and drug concentrations.
Main Results:
- Total CLCHDF was primarily dependent on Qe and unaffected by human serum albumin concentration.
- Diafiltration accounted for over 88% of ganciclovir removal, while adsorption contributed less than 9.4%.
- The blood-to-plasma ratio (R) remained consistent across all tested hematocrit levels and ganciclovir concentrations.
Conclusions:
- Diafiltration is the predominant mechanism for ganciclovir removal during CHDF.
- Hematocrit levels do not significantly alter the relationship between plasma and whole blood CLCHDF.
- CLCHDF of ganciclovir can be reliably estimated from Qe and R in in vitro settings.
Abstract:
Estimation of the continuous hemodiafiltration (CHDF) clearance (CLCHDF) 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 CLCHDF 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 CLCHDF, 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 CLCHDF 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 CLCHDF of GCV, rather than adsorption. Hematocrit levels might not affect the relationship between the plasma and blood CLCHDF of GCV, and the CLCHDF of GCV can be estimated from the Qe and R, at least in vitro.
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