In vitro analysis of factors affecting the continuous hemodiafiltration clearance of teicoplanin

Abstract

Background: In the treatment of sepsis, continuous hemodiafiltration (CHDF) and the administration of antibiotics such as teicoplanin (TEIC) are frequently performed in parallel. We aimed to clarify the factors influencing the CHDF clearance (CL_CHDF ) of TEIC using a polymethylmethacrylate (PMMA) membrane or a polyacrylonitrile and sodium methallyl sulfonate copolymer membrane coated with polyethylenimine (AN69ST). We also investigated whether the adsorption of TEIC onto the hemofilters inhibits the adsorption of interleukin (IL)-6 onto the membranes.

Methods: TEIC, human serum albumin (HSA), and IL-6 were incubated with pieces of hemofilter membranes and adsorption rates were calculated. The CL_CHDF , diafiltration rate, and adsorption rate of TEIC were calculated using an in vitro CHDF circuit model.

Results: The adsorption rates of TEIC onto the pieces of PMMA and AN69ST membranes ranged from 15.0% to 100% and from -10% to 5%, respectively. The adsorption rate of IL-6 was similar with or without TEIC. The CL_CHDF and adsorption rate of TEIC under PMMA-CHDF depended on HSA, but not on effluent flow rate (Qe). The CL_CHDF under AN69ST-CHDF depended on HSA and Qe. The observed CL_CHDF under AN69ST-CHDF was similar to the predicted value (the product of Qe and the plasma unbound fraction). The observed CL_CHDF under PMMA-CHDF was 2.0-7.8 times greater than the predicted value.

Conclusions: Adsorption mainly contributes to the CL_CHDF of TEIC using PMMA membranes, whereas diafiltration mainly contributes to the CL_CHDF of TEIC using AN69ST membranes. TEIC adsorption might not affect the adsorption of IL-6 onto PMMA membrane.

Keywords: clearance; continuous hemodiafiltration; polyacrylonitrile and sodium methallyl sulfonate copolymer; polymethylmethacrylate; teicoplanin.