Lindahl K, Schvarcz R, Bruchfeld A, Ståhle L
Division of Infectious Diseases, Department of Medicine, Karolinska Institute and Huddinge University Hospital, Stockholm, Sweden.
J Viral Hepat. 2004 Jan;11(1):84-7. doi: 10.1046/j.1365-2893.2003.00475.x.
Ribavirin in combination with interferon alpha-2 or pegylated interferon is the standard treatment for chronic hepatitis C. The current dosage recommendations for ribavirin are based on body weight (bw). Ribavirin is mainly eliminated by the kidneys and we have recently shown that ribavirin plasma concentrations are determined primarily by renal function. It is therefore reasonable to hypothesize that side-effects of ribavirin, i.e. anaemia, should be more closely related to plasma concentrations of ribavirin than to the dose per kg bw. A total of 108 consecutive patients eligible for treatment of chronic hepatitis C were studied. Ribavirin concentrations in plasma were measured by high-performance liquid chromatography (HPLC)-UV after solid-phase extraction in trough samples taken 4, 8 and 12 weeks after the treatment commenced. A total of 213 samples were obtained and the change in the haemoglobin level and the creatinine concentration was measured in addition to ribavirin. The dose of ribavirin per kg bw did not correlate with the drop in haemoglobin level induced by ribavirin. The concentration of ribavirin was non-linearly related to the drop in the haemoglobin level as revealed by fitting a standard Hill equation type dose-response curve. The half maximal drop in haemoglobin was obtained at 4.4 microm. The results from this study suggest that the anaemia induced by ribavirin depends primarily on the concentration of ribavirin, and not on the dose per kg bw. This lends further support to the idea that ribavirin should be dosed according to renal function.
利巴韦林联合干扰素α-2或聚乙二醇化干扰素是慢性丙型肝炎的标准治疗方法。目前利巴韦林的剂量推荐是基于体重（bw）。利巴韦林主要通过肾脏清除，我们最近发现利巴韦林的血浆浓度主要由肾功能决定。因此，合理推测利巴韦林的副作用，即贫血，应该与利巴韦林的血浆浓度比与每千克体重的剂量更密切相关。共研究了108例连续符合慢性丙型肝炎治疗条件的患者。在治疗开始后4、8和12周采集的谷值样本经固相萃取后，采用高效液相色谱（HPLC）-紫外法测定血浆中的利巴韦林浓度。共获得213个样本，除了利巴韦林外，还测量了血红蛋白水平和肌酐浓度的变化。每千克体重的利巴韦林剂量与利巴韦林引起的血红蛋白水平下降无关。通过拟合标准的希尔方程类型剂量反应曲线发现，利巴韦林浓度与血红蛋白水平下降呈非线性相关。血红蛋白下降一半时的浓度为4.4微摩尔。本研究结果表明，利巴韦林引起的贫血主要取决于利巴韦林的浓度，而不是每千克体重的剂量。这进一步支持了根据肾功能调整利巴韦林剂量的观点。
