A pharmacokinetic and pharmacodynamic comparison of a novel pegylated recombinant consensus interferon-α variant with peginterferon-α-2a in healthy subjects.

AIMS: The aims of the study were to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of a novel, pegylated recombinant human consensus interferon-α variant (PEG-IFN-SA) in healthy volunteers. A pharmacokinetic and pharmacodynamic comparison of PEG-IFN-SA and peginterferon-α-2a in healthy subjects was evaluated. METHODS: A randomized, dose-escalating, single administration dose phase I clinical study was conducted. Thirty healthy subjects received PEG-IFN-SA as a single dose of 0.5-2.0 μg kg(-1) by subcutaneous (s.c.) injection in four parallel groups. Eight subjects received peginterferon-α-2a as a single dose of 180 μg s.c. RESULTS: The incidence rates of adverse events for PEG-IFN-SA and peginterferon-α-2a were 29 of 30 and 7 of 8, respectively. The adverse events for PEG-IFN-SA were mild to moderate and similar to those of peginterferon-α-2a. Within 168 h after injection, the mean values of maximal concentration and area under the plasma concentration-time curve from time of dosing to 168 h [AUC(0-168h) ] for 2',5'-oligoadenylate, neopterin and β2 -microglobulin for PEG-IFN-SA at 1.5 μg kg(-1 ) s.c. were similar to or higher than those for peginterferon-α-2a at a dose of 180 μg s.c. After s.c. injection of PEG-IFN-SA at 1.5 μg kg(-1) , the mean geometric mean values of plasma half-life, time to maximal concentration, maximal concentration and AUC(0-168h) were 55.3 h, 26.9 h, 0.53 μg l(-1) and 44.0 μg l(-1)  h, respectively. CONCLUSIONS: The tolerance, pharmacokinetic and pharmacodynamic characteristics of PEG-IFN-SA support its administration by s.c. injection as a single dose of 1.5 μg kg(-1) or at 2.0 μg kg(-1) per week.