title: Single-dose pharmacokinetics, safety, and tolerability of albinterferon alfa-2b in subjects with end-stage renal disease on hemodialysis compared to those in matched healthy volunteers.
abstract: Albinterferon alfa-2b (albIFN) is being developed, in combination with ribavirin, for the treatment of hepatitis C virus infection. This study was designed to evaluate the pharmacokinetics, safety, and tolerability of a 900-μg dose of albIFN administered as a single subcutaneous injection in end-stage renal disease (ESRD) patients on hemodialysis and matched healthy volunteers (by age [±5 years], weight [±5 kg], and gender). The maximum concentration in plasma (C(max)) and the area under the concentration-time curve from time zero to infinity (AUC(0-∞)) were 42.8 ± 14.0 ng/ml and 16,414 ± 4,203 ng·h/ml, respectively, for healthy volunteers, while the C(max) and AUC(0-∞) were 49.9 ± 20.9 ng/ml and 18,919 ± 8,008 ng·h/ml, respectively, for ESRD patients. The geometric least-squares mean ratios were 1.15 (90% confidence interval [CI], 0.78, 1.68) for C(max) and 1.11 (90% CI, 0.83, 1.48) for AUC(0-∞). Adverse events were as expected for an interferon (e.g., flu-like symptoms), with the main laboratory adverse event being a decline in total white blood cell count, which was specifically related to a decline in the neutrophil count. This effect was somewhat greater in the ESRD patients, with the maximal decreases in neutrophil counts from those at the baseline being (-2.6 ± 0.32) × 10(9) and (-2.19 ± 0.58) × 10(9) cells/liter for the ESRD patients and the healthy volunteers, respectively. This study indicates no significant effect of renal failure on the pharmacokinetics of albIFN. Safety and tolerability were as expected for an interferon.
authors.affiliation: Novartis Institutes for Biomedical Research, East Hanover, NJ 07936, USA.
authors.forename: Denise B
authors.initials: DB
authors.lastname: Serra
authors.forename: Haiying
authors.initials: H
authors.lastname: Sun
authors.forename: Sylwia
authors.initials: S
authors.lastname: Karwowska
authors.forename: Jens
authors.initials: J
authors.lastname: Praestgaard
authors.forename: Atef
authors.initials: A
authors.lastname: Halabi
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Stein
mesh_terms: D000328:Adult; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C531108:albinterferon alfa-2b