title: Improved pharmacodynamics and pharmacokinetics after i.v. application of peginterferon alfa-2a in hepatitis C null responders.
abstract: OBJECTIVE
  Mechanisms of non-responsiveness to peginterferon alfa-2a are not completely understood. Inadequate plasma levels may contribute to reduced response. The aim of this prospective, multicentre, crossover, Phase 1 study was to evaluate the pharmacokinetics and viral kinetics of intravenous vs. subcutaneous peginterferon alfa-2a in patients with genotype 1 chronic hepatitis C infection who showed null response to previous peginterferon/ribavirin.
  
  
  METHODS
  Patients were randomized in four treatment arms to subcutaneous or intravenous peginterferon alfa-2a 180 μg, once or twice weekly for 2 weeks. After a washout phase of 6 weeks, patients first receiving intravenous administration switched to subcutaneous or vice versa for additional 2 weeks.
  
  
  RESULTS
  Intravenous administration of pegylated interferon resulted in a stronger and faster decline in HCV RNA than subcutaneous administration with a maximum decline of 1.17 log10 vs. 0.41 log10 or 1.32 log10 vs. 0.54 log10 after a once or twice weekly application, respectively. Pharmacokinetic studies revealed significantly higher maximum concentration (C(max))(0-12) h and C(max 0-7) d following intravenous administration, irrespective of dosing frequency A rapid rebound in HCV RNA was observed in all treatment arms. Adverse events occurred more frequently following intravenous administration.
  
  
  CONCLUSIONS
  Intravenous administration of peginterferon alfa-2a results in considerably higher plasma concentration and a stronger decline in HCV RNA and offers an interesting approach in order to overcome interferon non-responsive state in patients with full null response to previous peginterferon/ribavirin combination therapy.
authors: Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany.
authors: Balazs
authors: B
authors: Fülöp
authors: Jannsen-Cilag GmbH, Neuss, Germany.
authors: Michael
authors: M
authors: Biermer
authors: Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Hannover, Germany.
authors: Markus
authors: M
authors: Cornberg
authors: Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Hannover, Germany.
authors: Heiner
authors: H
authors: Wedemeyer
authors: Department of Gastroenterology, Hepatology & Endocrinology, Hannover Medical School, Hannover, Germany.
authors: Kerstin
authors: K
authors: Port
authors: Liver Center Checkpoint, Berlin, Germany.
authors: Renate
authors: R
authors: Heyne
authors: J.W. Goethe University Hospital, Frankfurt/M, Germany.
authors: Stefan
authors: S
authors: Zeuzem
authors: J.W. Goethe University Hospital, Frankfurt/M, Germany.
authors: Kai-Henrik
authors: KH
authors: Peiffer
authors: J.W. Goethe University Hospital, Frankfurt/M, Germany.
authors: Tania
authors: T
authors: Welzel
authors: Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany.
authors: Adam
authors: A
authors: Herber
authors: Institute for Interdisciplinary Medicine, Hamburg, Germany.
authors: Peter
authors: P
authors: Buggisch
authors: AMS Advanced Medical Services GmbH, Munich, Germany.
authors: Christoph
authors: C
authors: Moser
authors: Roche Pharma AG, Grenzach-Wyhlen, Germany.
authors: Sabine
authors: S
authors: Stoll
authors: Roche Pharma AG, Grenzach-Wyhlen, Germany.
authors: Ulrich
authors: U
authors: Alshuth
authors: Section of Hepatology, Department of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany.
authors: Thomas
authors: T
authors: Berg
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007275:Injections, Intravenous; D016898:Interferon-alpha / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics*; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a
keywords: crossover study; interferon; null response; viral dynamics