Pegylated Interferon-α2a Kinetics during Experimental HD: Impact of Permeability and Pore Size of Dialyzer

Abstract

Aims: To investigate changes in Pegasys blood levels in an experimental HD circuit during an “in vitro” HD session. In case that Pegasys levels change, to discern whether these changes are due to membrane clearance or adsorption. To assess the dynamic changes of Pegasys levels during the HD session and the impact of membranes with different permeability and pore size. Secondary, to compare Pegasys with other pegylated and nonpegylated -IFN. IFN preparations used: Pegasys (PEG-IFN-α2a): dose of 135 μg, Roferon (IFN-α2a) 18 MUI, Pegintron (PEG-IFN-α2b): dose of 100 μg (equivalent to the expected blood level measured in pts under active IFN treatment). Dialyzers. Polymethylmetacrylate (PMMA) dialyzers (Toray Ind., Japan) 1,6 m2 surface have been used : B3A type: pore size of 25 A and (low UF flux), BKP type:of 60 A and (high UF flux) and BKF type: pore size of 100 A and (UF rate of 25 ml/m2/mm Hg). HD circuit: All experiments were conducted under exactly the same conditions.employing the same HD machine (Toray) with controlled UF and bicarbonate dialysate. Closed circuit was established and the amount of IFN was injected in the blood bag (discarded for self-transfusions), homogenized and a pilot sample taken before the blood was recirculated throughout the HD circuit. The liquid ultrafiltrated was replaced for the circuit remains constant. Each experiment consists of a 3 hours conventional HD with standart parameters. Monitoring: venous presure, dialysate presure. Sampling. Pilot sample: (blood bag after IFN injection to measure IFN levels (no.1). 2 min. following establishment of the HD circuit, 15 min, 1 h, 2 h, and 3 h arterial and venous side. UF sample for 15 min and dialysate every hour. Blood samples are centrifuged, the plasma is isolated and then stored at 4 °C until measurement of IFN-αlevels. The ELISA employed to quantitate IFN-αblood levels is sensitive (detects reliably as low as < 5 pg/ml, that is at least 1 IU/ml). Summary of findings. In the HD circuit described Pegasys is not cleared through either low flux (B3A) or high flux (BKP). Arround 50% of Pegasys is cleared through a dialyzer with (BKF).The changes observed in the levels of Pegasys using BKF are apparently due to flow-through clearance rather than adherence to the dialyzer. Compared with Pegasys, Roferon (the non-pegylated IFN-α2a) and Pegintron (peg-IFN-α 2b) is washed-out within the 2 first hour of HD when using dialysers with either high flux (BKP) or (BKF). Through low flux (B3A) dialysers Roferon is not cleared sig. Conclusions: Pegasys is not cleared through either low flux (pore size: 25A) or high flux (pore size: 60A) PMMA dialyzers. Roferon and Pegintron are washed-out through high flux PMMA dialysers. The BKF clears completely Roferon and Pegintron but only partially Pegasys.