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.
摘要:
更昔洛韦(GCV)的连续血液透析滤过(CHDF)清除率(CLCHDF)的估算对于实现有效的治疗结果至关重要。这里,我们的目的是澄清渗滤的贡献,吸附,和血细胞比容水平在体外CHDF模型中的GCV的CLCHDF使用三个膜:聚丙烯腈和甲代烯丙基磺酸钠共聚物涂覆有聚乙烯亚胺(AN69ST);聚甲基丙烯酸甲酯(PMMA);和聚砜(PS)。以800、1500和3000mL/h的流出物流速(Qe)进行体外CHDF。初始GCV浓度为10μg/mL,而人血清白蛋白(HSA)的浓度为0或5g/dL。CLCHDF,渗滤率,并计算吸附率。使用具有0.5至100μg/mL的GCV的血液样品测定血细胞比容为0.1至0.5的GCV的全血与血浆比率(R)。体外CHDF实验使用AN69ST,PMMA,和PS膜显示,总CLCHDF值几乎与Qe相同,不受HSA浓度的影响。在所有条件下,渗滤率超过88.1±2.8%,而吸附率低于9.4±9.4%。R值为1.89±0.11,并且在所有血细胞比容水平和GCV浓度下相似。总之,渗滤主要有助于GCV的CLCHDF,而不是吸附。血细胞比容水平可能不会影响GCV的血浆和血液CLCHDF之间的关系,GCV的CLCHDF可以根据Qe和R来估计,至少在体外。