慢性
丙肝患者采用干扰素（IFN）-α治疗时，加用利巴韦林能够显著增强病毒学应答。法国Henri Mondor医院的Jean-Michel Pawlotsky博士及其同事旨在通过药物动力学评价利巴韦林对丙
肝病毒（HCV）的抗病毒作用，并评估这一抗病毒作用对IFN-α疗效的影响。
45例慢性丙肝（1b基因型）患者接受不同方案的IFN-α和/或利巴韦林治疗。多次采集血液标本，检测HCV RNA动力学和利巴韦林药物动力学。
结果显示，利巴韦林单一治疗可使大约一半患者出现显著、中度、早期、短暂的病毒负荷降低。出现这一作用与利巴韦林清除半衰期长、血清利巴韦林浓度高相关。患者进行每周三次常规IFN-α联合利巴韦林治疗时，利巴韦林的抗病毒作用可部分减少再次注射IFN-α前的反跳。反跳的程度与利巴韦林浓度呈负相关。随后，这些患者的病毒出现缓慢但显著的第二次降低，并且HCV-RNA得以清除。每日应用IFN-α单一治疗时加用利巴韦林，对病毒的二期降低无任何影响。
Pawlotsky博士等认为，利巴韦林对相当部分的慢性丙肝患者具有显著、中度、短暂的抗病毒作用。利巴韦林的抗病毒作用与其药物动力学相关，并通过增加初始应答率，可部分解释常规IFN-α与利巴韦林联合治疗的效果优于IFN-α单一治疗的原因。
Gastroenterology. 2004 Mar;126(3):703-14.
Antiviral action of ribavirin in chronic hepatitis C.
Pawlotsky JM, Dahari H, Neumann AU, Hezode C, Germanidis G, Lonjon I, Castera L, Dhumeaux D.
Background & Aims: In the patients with chronic hepatitis C, the addition of ribavirin to interferon (IFN)-alpha significantly increases the virologic responses. Our aim was to assess the antiviral action of ribavirin on hepatitis C virus (HCV) as a function of ribavirin pharmacokinetics and to evaluate the influence of this antiviral effect on IFN-alpha efficacy. Methods: Forty-five patients with chronic hepatitis C (genotype 1b) received various schedules of IFN-alpha and/or ribavirin administration. Frequent blood sampling was performed for HCV RNA kinetics and ribavirin pharmacokinetics assessment. Results: Ribavirin monotherapy induced a significant, moderate, early, and transient viral load decrease in approximately half of the patients. The occurrence of this effect was associated with longer ribavirin clearance half-lives and higher serum ribavirin concentrations. Ribavirin antiviral effect partly reduced the rebound preceding the second IFN-alpha injection in patients receiving standard IFN-alpha 3 times per week plus ribavirin. The magnitude of the rebound was inversely related to ribavirin concentrations. These patients subsequently experienced a slow, but significant, second slope of viral decrease and cleared HCV RNA. The addition of ribavirin to daily IFN-alpha monotherapy did not have any impact on the second phase of viral decline. Conclusions: Ribavirin exerts a significant, moderate, and transient antiviral effect in a significant proportion of patients with chronic hepatitis C. The antiviral effect of ribavirin correlates with ribavirin pharmacokinetics and is partly responsible for the improved efficacy of the combination of standard IFN-alpha and ribavirin compared with IFN-alpha monotherapy by increasing the incidence of the initial response.
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自动采集 2005-2-23
