Interferon (IFN)-based therapy is the recommended treatment for hepatitis C virus.
Because pegylated IFN (PEG-IFN) alfa-2a is administered subcutaneously, it is of interest
to determine the proportion of the dose that is absorbed from the subcutaneous (SC)
tissue and ultimately reaches systemic circulation.
The goal of this study was to characterize the absolute bioavailability of PEG-IFN
alfa-2a (40 kDa) after SC dosing (180 μg) and to evaluate the pharmacokinetics of
PEG-IFN alfa-2a after intravenous (IV) and SC administration.
In this parallel-group study, 18 participants were given a single IV dose of PEG-IFN
alfa-2a 90 μg and 18 participants received PEG-IFN alfa-2a 180 μg SC. Serum concentrations
of PEG-IFN alfa-2a were measured predose and serially until 312 hours after the first
dose. Pharmacokinetic parameters (CL/F, volume of distribution, Cmax, and Tmax) were estimated using noncompartmental methods. Bioavailability was calculated by
using the following formula: (AUCSC/AUCIV) · (doseIV/doseSC).
Eighteen healthy males received IV PEG-IFN alfa-2a, and an additional 18 healthy males
received SC PEG-IFN alfa-2a. Subjects in each group had comparable mean weight, height,
and body mass index. After IV administration of PEG-IFN alfa-2a (90 μg), there was
a slow decline in serum concentration, the mean rate of systemic clearance was low
at 126 mL/h, and the estimated mean volume of distribution at steady state was 9 L.
After SC administration of PEG-IFN alfa-2a 180 μg, absorption was sustained, with
mean Tmax occurring 102 hours after administration. The mean absolute bioavailability was 84%.
A higher rate of influenza-like symptoms was observed after IV administration, along
with decreased neutrophil counts, compared with subjects who underwent SC dosing.
Approximately 84% of a SC-administered dose of PEG-IFN alfa-2a reached the systemic
circulation in these male healthy volunteers. The slow absorption, restricted distribution,
and slow elimination of PEG-IFN alfa-2a resulted in sustained serum levels throughout
the 7-day dosing interval.