2005-雷替曲塞大鼠腹腔热灌注的药代动力学研究

翻译第1页©MedSciMonit,2005;11(1):BR1-5PMID:15614183©医学监测，2005；11（1）：br1-5分类号：15614183Received:2004.02.26Accepted:2004.08.19Published:2005.01.01收到:2004.02.26接受:2004.08.19发表:2005.01.01Authors’Contribution:AAStudyDesignBBDataCollectionCCStatisticalAnalysisDDataInterpretationEManuscriptPreparationFLiteratureSearchGFundsCollection作者的贡献:A个研究设计B数据收集C统计分析D维数据解释E手稿准备F文献检索G基金集合Background:背景:Materiel/Methods:材料/方法:AstudyoftheeffectoftemperatureonthepharmacokineticprofileofRaltitrexedadministeredbyintraperitonealrouteintherat温度的影响的研究药代动力学雷替曲塞由概况河鼠腹腔内的路线YvesBendavidABCDEFG,FrançoisA.LeblondABCDEFG,PierreDubéABCDEFG伊夫·ABCDEFG，弗朗索瓦·A,勒布隆·ABCDEFG,皮埃尔杜布·ABCDEFGDepartementofSurgery,Maisonneuve-RosemontHospital,UniversitédeMontréal,Montréal,Canada迈松纳夫-罗斯理科生，医院、大学医院,蒙特利尔,加拿大蒙特利尔,Summary总结Becauseheatcanimprovetheactivityofselecteddrugswhenadministeredheatedintheperito-nealcavityinthetreatmentofperitonealcarcinomatosisfromcolorectalorigin,thereisagreatin-teresttoevaluatenewcytotoxicagentsinthiscontext.Thepurposeofthisstudyistoassesstheef-fectofheatonthepharmacokineticprofileofRaltitrexedadministeredintraperitoneallyinrats.因为热量可以改善活动选择药物管理加热时腹腔腹膜从结肠直肠癌症治疗的起源,有一个极大的兴趣来评估新的细胞毒性剂在这个上下文。本研究的目的是评估的影响热的药代动力学资料雷替曲塞管理腹腔注射于老鼠。Rats#1to#40havebeensubmittedtodifferentdosesofintraperitonealRaltitrexed(2,4,and8mg/m2)atdifferentperfusiontemperatures(37,40and43°C).After25minutesofperfusion,peritonealfluid,portalandsystemicbloodwereharvestedandpreparedfordosageofRaltitrexed.Rats#41to#50havebeensubmittedto8mg/m2ofintraperitonealRaltitrexed(37and43°C)dur-ing25minutes.Then,asegmentofsmallbowelandasectionofResults:结果:Conclusions:结论:keywords:关键词:Full-textPDF:全文PDF:Wordcount:Tables:Figures:References:字数:表:人物:引用:Author’saddress:作者的地址:parietalperitoneumwereharvestedandpreparedforintracellulardosageofRaltitrexed.老鼠#1-#40已经提交给不同剂量腹腔雷替曲塞(2、4和8mg/m2)在不同灌注温度(37、40-43°C)。灌注25分钟后,腹水、门户和系统性的血液被收获,准备雷替曲塞的剂量。老鼠#41#50已经提交到8mg/m2的腹腔内雷替曲塞(37和43°C)在25分钟。然后,一段小肠和腹膜壁层的一部分被收获,准备雷替曲塞胞内剂量。ThedoseofRaltitrexedadministeredisadeterminantofitsconcentrationinperitonealperfusate,inportalveinbloodandinsystemicblood(p0.0002).Wenoticedthatperfusatetemperaturehadnosignificanteffectontheconcentrationofdrugintheportalveinblood(p=0.29)andinthesystemicblood(p=0.25).However,temperatureincreasedsignificantly(p0.04)theintracellularab-sorptionofRaltitrexed.雷替曲塞注射的剂量是一个行列式在腹膜灌流液的浓度,在门静脉血液和系统性的血液(p0.0002)。我们注意到灌注液温度没有明显影响门静脉血液中药物的浓度(p=0.29)和血液系统(p=0.25)。然而,温度显著增加(p0.04)雷替曲塞的细胞内吸收。BecausetheeffectofRaltitrexedisproportionaltoitsintracellularconcentration,itseemsclearthatRaltitrexedisofgreatestinterestwhenadministeredheatedintheperitoneumbecauseitcanreachgreaterintracellularconcentrationswithoutasignificantincreaseinsystemicconcentration,whichisresponsibleoftoxicity.因为雷替曲塞正比于其细胞内浓度的影响,显然雷替曲塞是最大利益的腹膜进行加热时,因为它可以达到更大的细胞内浓度没有显著增加系统性浓度,这是负责任的毒性。cancer•carcinomatosis•colorectal•intraperitonealchemotherapy•hyperthermia癌症•癌病•结直肠•腹腔化疗•热疗—37PierreDubé,MD,HôpitalMaisonneuve-Rosemont,5415boul.l’Assomption,Montréal(Québec),Canada,H1T2M4,e-mail:[e-mail]皮埃尔杜布、医学博士、医院、大道.第5415次迈松纳夫-罗斯“圣母升天节、蒙特利尔(魁北克)、加拿大、H1T2M4,电邮:[e-mail]/ClinicalMedicine•SCIExpanded•ISIAlertingSystem•IndexMedicus/MEDLINE•EMBASE/ExcerptaMedica•ChemicalAbstracts•IndexCopernicus当前内容/临床医学•SCI扩大•ISI报警系统•梅迪卡斯指数/联机医学文献分析和检索系统•荷兰医学文摘/节录本草•化学文摘•哥白尼索引翻译第2页BACKGROUND背景Untilrecentlyperitonealcarcinomatosis(PC)fromcolor-ectaloriginwasuniversallyconsideredtosignifyterminalillness.HoweverthisconcepthasbeenchallengedbysomewhohaveproventhatR0resection(resectionofallmacro-scopicimplants)followedbyintraperitonealchemother-apytotreatmicroscopicdiseasewasrewardedwithcurechancesof20%to80%atfiveyears[1–5].Intraperitonealchemotherapy(IC)isusedintreatingperitonealcarcino-matosisoriginatingfromcolorectalcancer(CRC).Whencombinedwithmaximaltumoralcytoreductioninselectivecases,curechancesrangefrom20%to80%atfiveyears[6,7].Withoutthisspecificadministrationrouteandevenwhencarcinomatosisislocalizedintheperitonealsurfacearea,curechancesareclosetozero[8].Anecdoticreportsmentionlongsurvivalfollowingmaximaltumoralcytore-duction,whethercombinedornotwithsystemicchemo-therapy,butgenerallyspeaking,themeansurvivalrateisapproximately1year[9].直到最近腹膜癌扩散(PC)在大肠癌起源普遍被认为是表示终端疾病。然而这一概念受到了挑战谁证明,弄清R0（传染数）切除(切除所有宏观植入)其次是腹腔内化疗治疗微观疾病得到治疗20%到80%的机会在五年[1-5]。腹腔内化疗(IC)用于治疗腹膜癌扩散来自结直肠癌(CRC)。当结合最大肿瘤细胞减灭术选择性情况下,治疗可能在五年内从20%到80%不等[6、7]。甚至没有这个特定的管理路线当癌症在腹膜表面局部区域,治愈的机会接近于零[8]。轶事的报告提到最大后长生还肿瘤细胞减灭术,是否结合全身化疗,但一般来说,平均成活率大约1年[9]。ICcanbeadministeredatroomtemperature[10].Itistheninitiatedassoonaftersurgeryaspossibleandcontinuedforafewdays.ItcallsfortheinstallationofTenkoffcathetersattimeofsurgery,withtreatmenteffectedbyperitonealdial-ysis.Prolongedbathing(afewdays)oftheabdominalcavi-tyseemstohamperthehealingprocess.Numerousanasto-moticleaksandabscessesareobservedinnormothermicallytreatedpatients.Thecytotoxicagents(CAs)mostfrequent-lyusedinnormothermictreatmentofCPoriginatingfromCRCareFluorouracilandMitomycin.Curecha