title: Pharmacokinetics, pharmacodynamics, and safety of peginterferon beta-1a in subjects with normal or impaired renal function.
abstract: Peginterferon beta-1a was efficacious in a Phase 3 relapsing multiple sclerosis trial, and its safety profile was consistent with other beta interferons. This study evaluated the impact of renal impairment on the pharmacokinetics and pharmacodynamics (neopterin elevation; a biomarker of pharmacological activity induced by interferon beta-1a) of peginterferon beta-1a following a single subcutaneous dose at 63 μg (n = 5) or 125 μg (n = 30). The results showed a fractional increase in area-under-the-concentration-time curve (AUC [30-53%]) and peak serum concentration (Cmax [26-42%]) in subjects with mild, moderate, and severe renal impairment, versus healthy subjects; AUC and Cmax were similar for healthy subjects and end-stage-renal-disease patients receiving hemodialysis. Pharmacokinetic simulation showed that the steady state concentration overlapped in the majority of healthy subjects and subjects with severe renal impairment. Neopterin baseline, peak concentration, and AUC increased as renal function decreased. Peginterferon beta-1a was well tolerated in all groups. These results do not warrant peginterferon beta-1a dose adjustment in subjects with renal impairment.
authors.affiliation: Biogen Idec Inc., Cambridge, MA, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.forename: Ali
authors.initials: A
authors.lastname: Seddighzadeh
authors.forename: Scott
authors.initials: S
authors.lastname: Stecher
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jaya
authors.initials: J
authors.lastname: Goyal
authors.forename: Mark
authors.initials: M
authors.lastname: Matson
authors.forename: Thomas
authors.initials: T
authors.lastname: Marbury
authors.forename: William
authors.initials: W
authors.lastname: Smith
authors.forename: Ivan
authors.initials: I
authors.lastname: Nestorov
authors.forename: Serena
authors.initials: S
authors.lastname: Hung
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D019798:Neopterin / Q000097:blood; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051437:Renal Insufficiency / Q000097:blood / Q000378:metabolism*
chemical_list: D000906:Antibodies; D011092:Polyethylene Glycols; D019798:Neopterin; D016899:Interferon-beta; C428112:peginterferon beta-1a
keywords: clinical trial; multiple sclerosis; pegylation