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HenriMondor医院的Jean-MichelPawlotsky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。次采集血液标本，检测HCVRNA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，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.2004Mar;126（3）:703-14.AntiviralactionofribavirininchronichepatitisC.PawlotskyJM,DahariH,NeumannAU,HezodeC,GermanidisG,LonjonI,CasteraL,DhumeauxD.Background&Aims:InthepatientswithchronichepatitisC,theadditionofribavirintointerferon（IFN）-alphasignificantlyincreasesthevirologicresponses.OuraimwastoassesstheantiviralactionofribavirinonhepatitisCvirus（HCV）asafunctionofribavirinpharmacokineticsandtoevaluatetheinfluenceofthisantiviraleffectonIFN-alphaefficacy.Methods:Forty-fivepatientswithchronichepatitisC（genotype1b）receivedvariousschedulesofIFN-alphaand/orribavirinadministration.FrequentbloodsamplingwasperformedforHCVRNAkineticsandribavirinpharmacokineticsassessment.Results:Ribavirinmonotherapyinducedasignificant,moderate,early,andtransientviralloaddecreaseinapproximatelyhalfofthepatients.Theoccurrenceofthiseffectwasassociatedwithlongerribavirinclearancehalf-livesandhigherserumribavirinconcentrations.RibavirinantiviraleffectpartlyreducedthereboundprecedingthesecondIFN-alphainjectioninpatientsreceivingstandardIFN-alpha3timesperweekplusribavirin.Themagnitudeofthereboundwasinverselyrelatedtoribavirinconcentrations.Thesepatientssubsequentlyexperiencedaslow,butsignificant,secondslopeofviraldecreaseandclearedHCVRNA.TheadditionofribavirintodailyIFN-alphamonotherapydidnothaveanyimpactonthesecondphaseofviraldecline.Conclusions:Ribavirinexertsasignificant,moderate,andtransientantiviraleffectinasignificantproportionofpatientswithchronichepatitisC.TheantiviraleffectofribavirincorrelateswithribavirinpharmacokineticsandispartlyresponsiblefortheimprovedefficacyofthecombinationofstandardIFN-alphaandribavirincomparedwithIFN-alphamonotherapybyincreasingtheincidenceoftheinitialresponse.
