Single-dose pharmacokinetics and safety of pegylated interferon-alpha2b in patients with chronic renal dysfunction.
This study evaluates the pharmacokinetics and safety of pegylated interferon-alpha2b (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 microg/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 CL(CR) declined. All subjects reported at least one adverse event, which were typical of those reported after alpha-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, AUCand Cmax 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 accountsfor less than half of its total clearance. Hemodialysis did not affect PEG-Intron apparent clearance.
D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D006526:Hepatitis C / Q000517:prevention & control; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D006435:Renal Dialysis; D012720:Severity of Illness Index
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a