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Pegylated interferon‐α2a kinetics during experimental haemodialysis: impact of permeability and pore size of dialysers
Author(s) -
Barril G.,
Quiroga J. A.,
Sanz P.,
RodrìguezSalvanés F.,
Selgas R.,
Carreño V.
Publication year - 2004
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2004.02014.x
Subject(s) - medicine , kinetics , permeability (electromagnetism) , edetic acid , urology , gastroenterology , pharmacology , biochemistry , membrane , chemistry , physics , quantum mechanics
Summary Background : Therapeutics in end‐stage renal disease (ESRD) patients undergoing haemodialysis (HD) has to consider potential drug clearance during the dialysis procedure. Pegylated interferon‐ α (PEG‐IFN‐ α ), a middle‐size protein drug active against viral hepatitis, allows convenient once‐weekly dosing due to prolonged plasma half‐life. Aim : To investigate the impact of permeability and dialyser pore size on PEG‐IFN‐ α blood levels during experimental HD. Methods : Polymethylmetacrylate (PMMA) membrane 1.6 m 2 dialysers with three different permeabilities/pore sizes were selected. Results : A 40 kDa PEG‐IFN‐ α 2a (PEGASYS) was not cleared (< 5%) through low‐flux/small pore size (25 Å;B3A) and high‐flux/middle‐large pore size (60 Å;BKP) dialysers, and was partially (≈15%) through intermediate permeability/large pore size (100 Å;BKF) dialysers. In contrast, unmodified 17 kDa IFN‐ α 2a(Roferon‐A) was removed (65%–95%) through BKP or BKF, but not B3A, PMMA dialysers. Moreover, 12 kDaPEG‐IFN‐ α 2b(PegIntron) was cleared (40%–80%) through PMMA dialysers with pore sizes ≥ 60 Å. When B3A or BKP were replaced every hour PEG‐IFN‐ α 2a plasma levels remained constant throughout three experimental‐HD‐sessions, but PEG‐IFN‐ α 2b was cleared partially every BKP replacement. Porosity differ among high‐flux dialysers. Neither PEG‐IFN‐ α 2a nor PEG‐IFN‐ α 2b were removed after three HD sessions through (27/31/33 Å) pore size polysulphone dialysers. Although PEG‐IFN‐ α 2a was not cleared through middle pore‐size (43 Å/AN69ST) polyacrylonitrile dialyser, PEG‐IFN‐ α 2b was partially removed. Conclusions : The pharmacokinetics of Peg‐IFN‐ α may vary in a patient on dialysis.