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

ABSTRACTAlbinterferon 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 (Cmax) and the area under the concentration-time curve from time zero to infinity (AUC0-∞) were 42.8 ± 14.0 ng/ml and 16,414 ± 4,203 ng·h/ml, respectively, for healthy volunteers, while theCmaxand AUC0-∞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) forCmaxand 1.11 (90% CI, 0.83, 1.48) for AUC0-∞. 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) × 109and (−2.19 ± 0.58) × 109cells/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.