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Clin Gastroenterol Hepatol. 2004 Apr;2(4):337-9.

Marked elevation of erythrocyte ribavirin levels in interferon and ribavirin-induced anemia.

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1
Department of Pharmaceutical Sciences, University of Tsukuba, Ibaraki, Japan.

Abstract

BACKGROUND & AIMS:

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.

PMID:
15067629
DOI:
10.1016/s1542-3565(04)00064-3
[Indexed for MEDLINE]

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