title: Erythrocyte ribavirin concentration for assessing hemoglobin reduction in interferon and ribavirin combination therapy.
abstract: 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.
  
  
  METHODS
  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+/-1.5mg/kg/day.
  
  
  RESULTS
  Steady-state plasma and erythrocyte ribavirin concentrations were 8.9+/-2.6 and 1218+/-270muM, 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 (>/=1000muM) had greater Hb reduction compared to those with lower levels (<1000muM) (3.8+/-1.2g/dL versus 2.6+/-0.9g/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 (>/=1000muM).
  
  
  CONCLUSIONS
  We confirmed that erythrocyte ribavirin was strongly associated with Hb reduction in interferon and ribavirin combination therapy.
authors.affiliation: Department of Pharmaceutical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masato
authors.initials: M
authors.lastname: Homma
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Shibata
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumura
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ito
authors.forename: Yukinao
authors.initials: Y
authors.lastname: Kohda