PMID- 22858176
OWN - NLM
STAT- MEDLINE
DCOM- 20130205
LR  - 20181201
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 34
IP  - 9
DP  - 2012 Sep
TI  - Evaluation of the absolute bioavailability of pegylated interferon alfa-2a after 
      subcutaneous administration to healthy male volunteers: an open-label, 
      randomized, parallel-group study.
PG  - 1883-91
LID - S0149-2918(12)00430-4 [pii]
LID - 10.1016/j.clinthera.2012.07.003 [doi]
AB  - BACKGROUND: 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. OBJECTIVE: The goal of this study was to characterize the absolute 
      bioavailability of PEG-IFN alfa-2a (40 kDa) after SC dosing (180 mug) and to 
      evaluate the pharmacokinetics of PEG-IFN alfa-2a after intravenous (IV) and SC 
      administration. METHODS: In this parallel-group study, 18 participants were given 
      a single IV dose of PEG-IFN alfa-2a 90 mug and 18 participants received PEG-IFN 
      alfa-2a 180 mug 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, C(max), and T(max)) were estimated using 
      noncompartmental methods. Bioavailability was calculated by using the following 
      formula: (AUC(SC)/AUC(IV)) . (dose(IV)/dose(SC)). RESULTS: 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 mug), 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 mug, absorption was sustained, 
      with mean T(max) 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. CONCLUSIONS: 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.
CI  - Copyright (c) 2012 Elsevier HS Journals, Inc. All rights reserved.
FAU - Brennan, Barbara J
AU  - Brennan BJ
AD  - Hoffmann-La Roche Inc, Nutley, New Jersey 07110, USA. barbara.brennan@roche.com
FAU - Xu, Zhi-Xin
AU  - Xu ZX
FAU - Grippo, Joseph F
AU  - Grippo JF
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20120801
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Antiviral Agents)
RN  - 0 (Interferon-alpha)
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - Q46947FE7K (peginterferon alfa-2a)
SB  - IM
MH  - Adult
MH  - Antiviral Agents/administration & dosage/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Humans
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Interferon-alpha/administration & dosage/*pharmacokinetics
MH  - Male
MH  - Middle Aged
MH  - Polyethylene Glycols/administration & dosage/*pharmacokinetics
MH  - Recombinant Proteins/administration & dosage/pharmacokinetics
MH  - Tissue Distribution
MH  - Young Adult
EDAT- 2012/08/04 06:00
MHDA- 2013/02/06 06:00
CRDT- 2012/08/04 06:00
PHST- 2012/05/25 00:00 [received]
PHST- 2012/07/07 00:00 [revised]
PHST- 2012/07/10 00:00 [accepted]
PHST- 2012/08/04 06:00 [entrez]
PHST- 2012/08/04 06:00 [pubmed]
PHST- 2013/02/06 06:00 [medline]
AID - S0149-2918(12)00430-4 [pii]
AID - 10.1016/j.clinthera.2012.07.003 [doi]
PST - ppublish
SO  - Clin Ther. 2012 Sep;34(9):1883-91. doi: 10.1016/j.clinthera.2012.07.003. Epub 
      2012 Aug 1.