Single-dose pharmacokinetics and safety of pegylated interferon-α2b in patients with chronic renal dysfunction

This study evaluates the pharmacokinetics and safety of pegylated interferon-α2b (PEG-Intron) following a single- dose 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 by up 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.