Pegylated interferon-alpha2a kinetics during experimental haemodialysis: impact of permeability and pore size of dialysers.
BACKGROUND
Therapeutics in end-stage renal disease (ESRD) patients undergoing haemodialysis (HD) has to consider potential drug clearance during the dialysis procedure. Pegylated interferon-alpha (PEG-IFN-alpha), a middle-size protein drug active against viral hepatitis, allows convenient once-weekly dosing due to prolonged plasma half-life.


OBJECTIVE
To investigate the impact of permeability and dialyser pore size on PEG-IFN-alpha blood levels during experimental HD.


METHODS
Polymethylmetacrylate (PMMA) membrane 1.6 m2 dialysers with three different permeabilities/pore sizes were selected.


RESULTS
A 40 kDa PEG-IFN-alpha2a (PEGASYS) was not cleared (< 5%) through low-flux/small pore size (25 A;B3A) and high-flux/middle-large pore size (60 A;BKP) dialysers, and was partially (approximately 15%) through intermediate permeability/large pore size (100 A;BKF) dialysers. In contrast, unmodified 17 kDa IFN-alpha2a(Roferon-A) was removed (65%-95%) through BKP or BKF, but not B3A, PMMA dialysers. Moreover, 12 kDa PEG-IFN-alpha2b(PegIntron) was cleared (40%-80%) through PMMA dialysers with pore sizes > or = 60 angstroms. When B3A or BKP were replaced every hour PEG-IFN-alpha2a plasma levels remained constant throughout three experimental-HD-sessions, but PEG-IFN-alpha2b was cleared partially every BKP replacement. Porosity differ among high-flux dialysers. Neither PEG-IFN-alpha2a nor PEG-IFN-alpha2b were removed after three HD sessions through (27/31/33 A) pore size polysulphone dialysers. Although PEG-IFN-alpha2a was not cleared through middle pore-size (43 A/AN69ST) polyacrylonitrile dialyser, PEG-IFN-alpha2b was partially removed.


CONCLUSIONS
The pharmacokinetics of Peg-IFN-alpha may vary in a patient on dialysis.
Barril
G
G
Department of Nephrology, Hospital U. de la Princesa, Madrid, Spain. gbarril@wanadoo.es
Quiroga
J A
JA
Sanz
P
P
Rodrìguez-Salvanés
F
F
Selgas
R
R
Carreño
V
V
D000998:Antiviral Agents / Q000493:pharmacokinetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005374:Filtration; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics*; D010539:Permeability; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D019904:Polymethyl Methacrylate; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000295:instrumentation
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D019904:Polymethyl Methacrylate; C100416:peginterferon alfa-2a