在干扰素和利巴韦林诱导的贫血中，红细胞利巴韦林水平显著升高。

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

作者信息

Homma Masato, Matsuzaki Yasushi, Inoue Yoichi, Shibata Minoru, Mitamura Keiji, Tanaka Naomi, Kohda Yukinao

机构信息

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

出版信息

Clin Gastroenterol Hepatol. 2004 Apr;2(4):337-9. doi: 10.1016/s1542-3565(04)00064-3.

DOI:10.1016/s1542-3565(04)00064-3

PMID:15067629

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.

摘要

背景与目的

为阐明血液中利巴韦林的分布对利巴韦林所致贫血的影响，在采用干扰素和利巴韦林联合疗法根除丙型肝炎病毒（HCV）的过程中，研究了红细胞内利巴韦林浓度与血液学参数变化之间的关系。

方法

9例HCV RNA阳性患者接受联合治疗，利巴韦林剂量为11.3±1.2mg·kg⁻¹·d⁻¹。测定血浆及红细胞中利巴韦林及其磷酸化代谢产物的血药浓度。

结果

在开始治疗的3 - 4周内，血浆和红细胞中的利巴韦林血药浓度分别逐渐升高至稳态水平，分别为8.8±1.4μmol/L和1389±371μmol/L。发现红细胞磷酸化代谢产物水平（1215±302μmol/L）极高，即占所测红细胞利巴韦林浓度的87%。相比之下，血浆中磷酸化代谢产物水平无法检测到。红细胞利巴韦林浓度与血红蛋白降低之间存在正相关（r = 0.620，P < 0.001）。