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.