·6·安徽医药AnhuiMedicalandPharmaceuticalJournal2012Jan;16(1)
[7]WhitleyRJ,GnannJWJr.Disseminatedherpeszosterintheimmu-nocompromisedhost:acomparativetrialofacyclovirandVidarabine
[J].JInfectDis,1992,165(3):450.[8]PerryCM,WagstaffAJ.Famciclovir:areviewofitspharmacologicalpropertiesandtherapeuticefficacyinherpesvirusinfections[J].1995,50(2):396-15.Drugs,
[9]张群寿.泛昔洛韦治疗带状疱疹50例[J].华西药学杂志,
2008,23(2):243.[10]DeClercqE.DiscoveryanddevelopmentofBVDU(brivudin)asatherapeuticforthetreatmentofherpeszoster[J].BiochemPharma-col,2004,68(12):2301-15.[11]WassilewSW,WutzlerP.Oralbrivudinincomparisonwithacyclovir
forimprovedtherapyofherpeszosterinimmunocompetentpatients:resultsofarandomized,double-blind,multicenteredstudy[J].Anti-viralRes,2003,59(1):49-56.
[12]OkudaH,OguraK,KatoA,etal.Apossiblemechanismofeighteen
patientdeathscausedbyinteractionsofsorivudine,anewantiviral
withoral5-fluorouracilprodrugs[J].JPharmacolExpTher,drug,
完成。为了确定口服FV100的安全性及药代动力学,进行了
3项随机,双盲,安慰剂对照临床试验。实验结果表明FV100经吸收后可以迅速的转化为Cf1743,而且在24h之后其浓度还高于抗病毒活性要求的EC50。Cf1743的肾脏清除率较低。FV100对所有的受试者都表现出较好的耐受性。这些药代动力学和安全性的试验结果可以支持FV100继续其治疗带状
[22]
疱疹和预防带状疱疹后神经痛的研究。治疗带状疱疹的
[23]
双盲对照的二期临床试验目前还在进行中。随机、
图1Cf1743
的分子结构
1998,287(2):791-9.
[13]WhitleyRJ.A70-year-oldwomanwithshingles:reviewofherpes
zoster[J].JAMA,2009,302(1):73-80.
[14]HostetlerKY.Alkoxyalkylprodrugsofacyclicnucleosidephospho-natesenhanceoralantiviralactivityandreducetoxicity:currentstateoftheart[J].AntiviralRes,2009,82(2):A84-98.[15]LanierR,TrostL,TippinT,etal.DevelopmentofCMX001forthe
TreatmentofPoxvirusInfections[J].Viruses,2010,2(12):2740-62.
[16]Williams-AzizSL,HartlineCB,HardenEA,etal.Comparativeactiv-itiesoflipidestersofcidofovirandcycliccidofoviragainstreplica-tionofherpesvirusesinvitro[J].AntimicrobAgentsChemother,2005,49(9):3724-33.[17]RobertsonA.SafetyandpharmacokineticanalysisofCMX001:re-sultsfromaFTIHdoseescalationstudy(CMX001-102)[C].IDSAAnnualMeeting,Philadelphia,2009.
[18]CruteJJ,GrygonCA,HargraveKD,etal.Herpessimplexvirusheli-case-primaseinhibitorsareactiveinanimalmodelsofhumandisease
[J].NatMed,2002,8(4):386-91.[19]ChonoK,KatsumataK,KontaniT,etal.ASP2151,anovelhelicase-possessesantiviralactivityagainstvaricella-zosterprimaseinhibitor,
virusandherpessimplexvirustypes1and2[J].JAntimicrobChe-mother,2010,65(8):1733-41.[20]McGuiganC,YarnoldCJ,JonesG,etal.Potentandselectiveinhibi-tionofvaricella-zostervirus(VZV)bynucleosideanalogueswithan
unusualbicyclicbase[J].JMedChem,1999,42(22):4479-84.[21]McGuiganC,PathiranaRN,MiglioreM,etal.Preclinicaldevelop-mentofbicyclicnucleosideanaloguesaspotentandselectiveinhibi-torsofvaricellazostervirus[J].JAntimicrobChemother,2007,60(6):1316-30.[22]HelenSP,MarkM,GeorgeA,etal.PharmacokineticsandSafetyof
FV-100,aNovelOralAnti-HerpesZosterNucleosideAnalogue,Ad-ministeredinSingleandMultipleDosestoHealthyYoungAdultandElderlyAdultVolunteers[J].AntimicrobAgentsChemother,2011,55(6):2847-54.[23]McGuiganC,BalzariniJ.FV100asanewapproachforthepossibletreatmentofvaricella-zostervirusinfection[J].JAntimicrobChe-mother,2009,64(4):671-3.[24]GilbertC,Bestman-SmithJ,BoivinG.Resistanceofherpesvirusesto
antiviraldrugs:clinicalimpactsandmolecularmechanisms[J].
DrugResistanceUpdates,2002,5:88-114.
(收稿日期:2011-04-20)
图2FV100的分子结构
3
结论
由于器官移植、艾滋病等原因,免疫妥协患者的人数越来越多,从而导致了临床上感染疱疹病毒的人群显著增加。随着阿昔洛韦等抗病毒药物的广泛应用,临床上分离到多种耐
[24]
药病毒株,耐药病毒株的出现迫切的要求我们研制新的抗病毒药物以解决这一问题。人类基因组计划的完成和全球基
比如微阵列等,都对抗病毒药物的研发产因监测技术的发展,
生了新的思路。通过抑制病毒蛋白不是抗病毒药物研发的唯一途径,以细胞的蛋白,甚至沉默病毒基因等为靶标可以提供新的途径来降低疱疹病毒对人类的危害。参考文献:
[1]ZerboniL,KuCC,JonesCD,etal.Varicella-zostervirusinfectionof
humandorsalrootgangliainvivo[J].ProcNatlAcadSci,2005,102(18):6490-5.[2]王
松,陈家骅.带状疱疹后神经痛的诊疗现状及进展[J].安
2009,13(1):91-2.徽医药,
[3]MuellerNH,GildenDH,CohrsRJ,etal.Varicella-zostervirusinfec-molecularpathogenesisofdisease,andlaten-tion:clinicalfeatures,
cy[J].NeurolClin,2008,26(3):675-97.
[4]GrossG,SchoferH,WassilewS,etal.Herpeszosterguidelineofthe
GermanDermatologySociety(DDG)[J].JClinVirol,2003,26(3):277-89.
[5]EnrightAM,ProberC.Antiviraltherapyinchildrenwithvaricella
zostervirusandherpessimplexvirusinfections[J].Herpes,2003,10(2):32-7.
[6]AdairJC,GoldM,BondRE.Acyclovirneurotoxicity:clinicalexperi-enceandreviewoftheliterature[J].SouthMedJ,1994,87(12):1227-31.