title: Marked elevation of erythrocyte ribavirin levels in interferon and ribavirin-induced anemia.
abstract: OBJECTIVE
  To elucidate the effects of blood ribavirin disposition on ribavirin-induced anemia, the relationship between erythrocyte ribavirin concentration and change in hematologic parameters was examined in interferon and ribavirin combination therapy for HCV eradication.
  
  
  METHODS
  Nine HCV RNA-positive patients were treated with combination therapy including 11.3 +/- 1.2 mg.kg(-1).day(-1) of ribavirin. Blood concentrations of ribavirin and its phosphorylated metabolites were measured in plasma as well as erythrocyte.
  
  
  RESULTS
  Blood ribavirin concentrations gradually increased to steady-state levels of 8.8 +/- 1.4 micromol/L and 1389 +/- 371 micromol/L in plasma and erythrocytes, respectively, within 3-4 weeks of initiating therapy. Erythrocyte phosphorylated metabolite levels (1215 +/- 302 micromol/L) were found to be exceedingly high, i.e., 87% of the measured erythrocyte ribavirin concentration. In contrast, plasma phosphorylated metabolite levels were undetectable. Positive correlation was found to exist between erythrocyte ribavirin concentrations and a decrease in hemoglobin (r = 0.620, P < 0.001).
  
  
  CONCLUSIONS
  We concluded that marked elevation of erythrocyte ribavirin including its phosphorylated metabolites was associated with hemoglobin reduction, leading to interferon and ribavirin-induced anemia.
authors.affiliation: Department of Pharmaceutical Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Homma
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Inoue
authors.forename: Minoru
authors.initials: M
authors.lastname: Shibata
authors.forename: Keiji
authors.initials: K
authors.lastname: Mitamura
authors.forename: Naomi
authors.initials: N
authors.lastname: Tanaka
authors.forename: Yukinao
authors.initials: Y
authors.lastname: Kohda
mesh_terms: D000740:Anemia / Q000139:chemically induced* / Q000503:physiopathology; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood* / Q000378:metabolism; D018570:Risk Assessment; D012494:Sampling Studies; D012720:Severity of Illness Index
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D012254:Ribavirin