Role of erythrocytes as a reservoir for ribavirin and relationship with adverse reactions in the early phase of interferon combination therapy for chronic hepatitis C virus infections

Hidetsugu Saito, Shinichiro Tada, Hirotoshi Ebinuma, Hiromasa Ishii, Kazuo Kashiwazaki, Masahiko Takahashi, Nobuhiro Tsukada, Jiro Nishida, Shin Tanaka, Hiroshi Shiozaki, Toshifumi Hibi

Research output: Contribution to journalArticle

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Abstract

We investigated the relationship between serum ribavirin concentrations and clearance, as well as therapeutic efficacy and adverse reactions, in 97 Japanese patients with chronic hepatitis C virus infections treated with a 6-month course of high-dose alpha2b interferon (6 million units/day) plus ribavirin (600 to 800 mg/day) combination therapy. This randomized trial showed that the saturation of ribavirin uptake after taking ribavirin capsules does not occur within a dose range of 600 to 800 mg/day, which is a standard dosage used clinically in Japan. Serum ribavirin concentrations and clearance did not correlate with sustained virological response rates. Fourteen patients discontinued therapy because of adverse reactions, and sustained virological response rates were significantly reduced by discontinuation of therapy, while dose reduction of ribavirin did not alter the therapeutic effects. Ribavirin concentrations after 1 week and ribavirin clearance were significantly correlated with discontinuation of ribavirin; however, a multiple-regression analysis revealed that only hemoglobin concentration, but not ribavirin clearance, was a significant factor for discontinuation of therapy (odds ratio, 0.514; 95% confidence interval, 0.311 to 0.85; P = 0.0095). It appears that peripheral erythrocytes may act as a reservoir for ribavirin and regulate serum ribavirin levels in the very early phase of treatment.

Original languageEnglish
Pages (from-to)3562-3568
Number of pages7
JournalJournal of Clinical Microbiology
Volume44
Issue number10
DOIs
Publication statusPublished - 2006 Oct

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Ribavirin
Chronic Hepatitis C
Virus Diseases
Hepacivirus
Interferons
Erythrocytes
Therapeutics
Serum
Therapeutic Uses
Capsules
Japan
Hemoglobins
Odds Ratio
Regression Analysis
Confidence Intervals

ASJC Scopus subject areas

  • Microbiology (medical)
  • Microbiology

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Role of erythrocytes as a reservoir for ribavirin and relationship with adverse reactions in the early phase of interferon combination therapy for chronic hepatitis C virus infections. / Saito, Hidetsugu; Tada, Shinichiro; Ebinuma, Hirotoshi; Ishii, Hiromasa; Kashiwazaki, Kazuo; Takahashi, Masahiko; Tsukada, Nobuhiro; Nishida, Jiro; Tanaka, Shin; Shiozaki, Hiroshi; Hibi, Toshifumi.

In: Journal of Clinical Microbiology, Vol. 44, No. 10, 10.2006, p. 3562-3568.

Research output: Contribution to journalArticle

Saito, Hidetsugu ; Tada, Shinichiro ; Ebinuma, Hirotoshi ; Ishii, Hiromasa ; Kashiwazaki, Kazuo ; Takahashi, Masahiko ; Tsukada, Nobuhiro ; Nishida, Jiro ; Tanaka, Shin ; Shiozaki, Hiroshi ; Hibi, Toshifumi. / Role of erythrocytes as a reservoir for ribavirin and relationship with adverse reactions in the early phase of interferon combination therapy for chronic hepatitis C virus infections. In: Journal of Clinical Microbiology. 2006 ; Vol. 44, No. 10. pp. 3562-3568.
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