title: 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.
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.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. hsaito@sc.itc.keio.ac.jp
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Saito
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Tada
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Ebinuma
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Ishii
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kashiwazaki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tsukada
authors.forename: Jiro
authors.initials: J
authors.lastname: Nishida
authors.forename: Shin
authors.initials: S
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shiozaki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects* / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin