Improved pharmacodynamics and pharmacokinetics after i.v. application of peginterferon alfa-2a in hepatitis C null responders.
Liver Int
; 35(10): 2275-84, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-25801095
ABSTRACT
BACKGROUND & AIM:
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.CONCLUSION:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Polietilenoglicóis
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RNA Viral
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Interferon-alfa
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Carga Viral
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Hepatite C Crônica
Tipo de estudo:
Clinical_trials
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Observational_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article