Erythrocyte ribavirin concentration for assessing hemoglobin reduction in interferon and ribavirin combination therapy

Background: Ribavirin-induced hemolytic anemia is one of the important adverse effects for the premature cessation of interferon and ribavirin combination therapy for hepatitis C virus clearance. To elucidate the mechanism of this matter, we examined the effects of plasma and erythrocyte ribavirin concentration on hemoglobin (Hb) reduction to assess hemolytic anemia in this combination therapy. Method: Nineteen patients, treated with the interferon alpha-2b and ribavirin combination therapy, were included. Plasma and erythrocyte ribavirin concentrations were monitored for the first 28 days of the combination therapy, in relation to changes in hematological parameters, Hb and hematocrit values. The initial dose of ribavirin was 11.5 +/- 1.5 mg/kg/day. Results: Steady-state plasma and erythrocyte ribavirin concentrations were 8.9 +/- 2.6 and 1218 +/- 270 mu M, respectively. Significant correlation was observed between erythrocyte ribavirin and Hb reduction (r = 0.360, p < 0.05), but not between plasma ribavirin and Hb reduction. The patients with higher levels of erythrocyte ribavirin (> 1000 mu M) had greater Hb reduction compared to those with lower levels (< 1000 mu M) (3.8 +/- 1.2 g/dL versus 2.6 +/- 0.9 g/dL, p < 0.05). Nine cases out of 12 patients who developed anemia within the first 28 days of the combination therapy had higher levels of erythrocyte ribavirin (> 1000 mu M). Conclusion: We confirmed that erythrocyte ribavirin was strongly associated with Hb reduction in interferon and ribavirin combination therapy. (c) 2005 Elsevier Ireland Ltd. All rights reserved.