Article date: April 2015
By: Li Zheng, Mao Ping Li, Zhong Ping Gou, Ying Wang, Nan Xu, Yong Ming Cai, Hua Luo, in Volume 79, Issue 4, pages 650-659
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.
DOI: 10.1111/bcp.12528
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