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Journal of Clinical Microbiology, October 2006, p. 3562-3568, Vol. 44, No. 10
0095-1137/06/$08.00+0     doi:10.1128/JCM.00079-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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,1* Shinichiro Tada,1 Hirotoshi Ebinuma,1 Hiromasa Ishii,1 Kazuo Kashiwazaki,2 Masahiko Takahashi,3 Nobuhiro Tsukada,4 Jiro Nishida,5 Shin Tanaka,6 Hiroshi Shiozaki,7 and Toshifumi Hibi1

Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan,1 Tachikawa Hospital, 4-2-22 Nishiki-machi, Tachikawa, Tokyo 190-8531, Japan,2 Tokyo Metropolitan Hiroo Hospital, 2-34-10 Ebisu, Shibuya-ku, Tokyo 150-0013, Japan,3 Tokyo Metropolitan Saisei-kai Central Hospital, 1-4-17 Mita, Minato-ku, Tokyo 108-0073, Japan,4 Tokyo Dental Collage Ichikawa General Hospital, 5-11-13 Sugano, Ichikawa, Chiba 272-8518, Japan,5 National Hospital Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan,6 Tochigi Saisei-kai Utsunomiya Hospital, 911-1 Takebayashi-cho, Utsunomiya, Tochigi 321-0974, Japan7

Received 13 January 2006/ Returned for modification 20 May 2006/ Accepted 2 August 2006

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.

* Corresponding author. Mailing address: Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Phone: 81 3 3353 1211, ext. 62894. Fax: 81 3 3351 8705. E-mail: hsaito{at}sc.itc.keio.ac.jp.

Journal of Clinical Microbiology, October 2006, p. 3562-3568, Vol. 44, No. 10
0095-1137/06/$08.00+0     doi:10.1128/JCM.00079-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chan, A. H., Partovi, N., Ensom, M. H. (2009). The Utility of Therapeutic Drug Monitoring for Ribavirin in Patients with Chronic Hepatitis C--A Critical Review. The Annals of Pharmacotherapy 43: 2044-2063 [Abstract] [Full Text]  


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