Single-Dose Pharmacokinetics and Safety of Pegylated Interferon-Alpha 2b in Patients with Chronic Renal Dysfunction

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 (AUCtf', Cmax' and t1/2) increased progressively as CLcr 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 CLCR < 30 ml/min, AUC and Cmax 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 CLCR' renal clearance accounts for less than half of its total clearance. Hemodialysis did not affect PEG‐Intron apparent clearance.