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Single‐Dose Pharmacokinetics and Safety of Pegylated Interferon‐α2b in Patients with Chronic Renal Dysfunction
Author(s) -
Gupta Samir K.,
Pittenger Amy L.,
Swan Suzanne K.,
Marbury Thomas C.,
Tobillo Emlyn,
Batra Vijay,
Sack Marshall,
Glue Paul,
Jacobs Sheila,
Affrime Melton
Publication year - 2002
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127002237996
Subject(s) - pharmacokinetics , medicine , hemodialysis , renal function , adverse effect , pharmacology , urology , pegylated interferon , gastroenterology , immunology , ribavirin , virus , hepatitis c virus
This study evaluates the pharmacokinetics and safety of pegylated interferon‐α2b (PEG‐Intron) following a singledose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open‐label, single‐dose, parallel‐group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis‐dependent group. They received 1 μg/kg PEG‐Intron subcutaneously after a 10‐hour fast. Pharmacokinetic and safety assessments were performed up to 168 hours postdose. Hemodialysis patients had a second PEG‐Intron dose 12 hours prior to a hemodialysis session. PEG‐Intron pharmacokinetic parameters (AUC tf' , C max' and t 1/2 ) increased progressively as CL cr declined. All subjects reported at least one adverse event, which were typical of those reported after α‐interferon administration (e.g., flu‐like symptoms, headache). Single‐dose PEG‐Intron administration to volunteers with normal renal function and chronic renal impairment was safe and well tolerated. In patients with CL CR < 30 ml/min, AUC and C max values were increased 90% compared with controls, while half‐life was increased byup to 40% over controls. Based on the relationship between PEG‐Intron apparent clearance and CL CR' renal clearance accounts for less than half of its total clearance. Hemodialysis did not affect PEG‐Intron apparent clearance.