丁酸氯维地平注射乳的药理及临床研究

ChineseJournalofNewDrugs2010,19(12)100320101912[]李灵,女,硕士研究生,联系电话:[phone],Emai:[e-mail][]毕开顺,男,博士,教授,研究方向:药物分析学联系电话:[phone],Emai:[e-mail]胡欣,男,主任药师,研究方向:药物分析学联系电话:[phone],Emai:[e-mail]1,2,1,2(1沈阳药科大学药学院,沈阳110016;2卫生部北京医院药剂科,北京100730)[]静脉注射用乳剂丁酸氯维地平能快速精确地控制血压,适用于不宜口服治疗或口服治疗无效的高血压患者由于药效短和较好的风险利益关系,该药已成为抗高血压治疗的新选择现对其药理作用临床研究及不良反应等做一综述[]丁酸氯维地平;高血压;药理作用;临床研究[]R972.4[]A[]1003-3734(2010)12-1003-04PharmacologyandclinicalstudiesofclevidipinebutyrateinjectableemulsionLILing1,2,BIKaishun1,HUXin2(1SchoolofPharmacy,ShenyangPharmaceuticalUniversity,Shenyang110016,China;2DepartmentofPharmacy,BeijingHospital,theMinistryofHealth,Beijing100730,China)[Abstract]Clevidipinebutyrateinjectableemulsioncancontrolbloodpressurequicklyandeffectively.Whenoraldrugtherapyisnotappropriateforbloodpressurecontro,litsrapidactionandgoodbenefittoriskprofilemaybeagoodalternativeforantihypertensivetreatmen.tInthisarticle,thepharmacologicaleffects,clinicalstudiesandadversedrugreactionsofclevidipinebutyrateinjectableemulsionweresummarized.[Keywords]clevidipinebutyrate;hypertension;pharmacologicaleffec;tclinicalstudy[1-6],,[3-5],[4][4](clevidipinebutyrate,:Cleviprex)200881FDA,Medicines,[7]1()4(2,3)2,61,43,5(),C21H23Cl2NO6,456.3,,1[7]1ChineseJournalofNewDrugs2010,19(12)1004201019122L[7-10],L[7],,(),[7,9-11]33.1[12],[9-10],,[10],10~15min[13][14],25%,10mgh-150%[7]0.4gkg-1min-1,2~4min4%~5%,5~15min[7],(48nmolmin-1kg-1),15min[13,15][14],3.2[16],[14]2min,10min,2,2~10min[17],,[7]1min,15min[7]5min10%[18]3799.5%[7,17]0.19Lkg-1,0.069Lmin-1kg-1[18],,,003Lh-1kg-1,9h,[7,13,19][13]44.1(ESCAPE1ESCAPE2),,ESCAPE1ESCAPE2105110,(ESCAPE1)(ESCAPE2)160mmHg4h140mmHg,178/77mmHg150/71mmHg30min15%,,0.4gkg-1min-1,90s3.2gkg-1min-1,1.5gkg-1min-18gkg-1min-130min~1h,(15%)92.5%91.8%,(17.3%20.4%,P0.0001)1~2min6min5.3min,,31.2%28.9%,11.2%8.7%(P0.0001),51%53%,41%49%ESCAPE19%2%,ESCAPE2,ESCAPE221%12%,ESCAPE1[7,11,20-21]3,(ECLIPSE),1512,(=268278)(=296283)(=188193),0.4gkg-1min-1,90s3.2gkg-1min-1,1.5gkg-1min-18gkg-1min-14.4~8.0gkg-1min-1ChineseJournalofNewDrugs2010,19(12)1005201019122h7528h(4.5mgh-1),,(P=0.0006,0.003),,,30d30d,3,3,(P=0.04)[7,22]91,(0.05,0.18,0.32,1.37,3.19,9.58gkg-1min-1),1.37gkg-1min-1,032gkg-1min-110%[15]4.2VELOCITY,126(180mmHg115mmHg)2mgh-1,3min,32mgh-1,18~96h,1h(ITR),30min203mmHg,142~173mmHg9.5mgh-1,21h2mgh-12(1.6%)3min3min5.9%,30min21.1%10.9min,4mgh-188.9%30min,7mgh-1118,975%6h,115(91.3%)39.7%,30.2%,95%(6.3%)(48%)(32%)(3.2%)8.9%[7,23]4.361,(2,4,8,16mgh-1),72h2mgh-1,3min,(25%),10mgh-150%[7]5[10][7,11,14]6CYP450CYP3A4CYP2C9,CYP2C19CYP3A4[24][25],,,[11],[7],7,,,,,[][1]ARONSONS,BOISVERTD,LAPPW.Isolatedsystolichypertensionisassociatedwithadverseoutcomesfromcoronaryarterybypassgraftingsurgery[J].AnesthAnalg,2002,94(5):1079-1084.[2]WEITZHH.Perioperativecardiaccomplications[J].MedClinNorthAm,2001,85(5):1151-1169.[3]ERSTADBL,BARLETTAJF.Treatmentofhypertensionintheperioperativepatient[J].AnnPharmacother,2000,34(1):66-79.[4]LESLIEJB.IncidenceandaetiologyofperioperativehypertensionChineseJournalofNewDrugs2010,19(12)100620101912[J].ActaAnaesthesiolScandSuppl,1993,37(99):5-9.[5]WEISSSJ,LONGNECKERDE.Perioperativehypertension:anoverview[J].CoronArteryDis,1993,4(5):401-406.[6]ESTAFANOUSFG,TARAZIRC.Systemicarterialhypertensionassociatedwithcardiacsurgery[J].AmJCardiol,1980,46(4):685-694.[7]TheMedicinesCompany.CLEVIPREX(clevidipinebutyrate)emulsion[EB/OL].[2009-04-23].=8664.[8]YIX,VIVIENB,LYNCHC,etal.ClevidipineblockadeofLtypeCa2+currents:steadystateandkineticelectrophysiologicalstudiesinguineapigventricularmyocytes[J].JCardiovascPharmacol,2000,36(5):592-600.[9]NORDLANDERM,SJOQUISTPO,ERICSSONH,etal.Pharmacodynamic,pharmacokineticandclinicaleffectsofclevidipine,anultrashortactingcalciumantagonistforrapidbloodpressurecontrol[J].CardiovascDrugRev,2004,22(3):227-250.[10]KIELERJENSENN,JOLINMELLGRD,NORDLANDERM,etal.Coronaryandsystemichemodynamiceffectsofclevidipine,anultrashortactingcalciumantagonist,fortreatmentofhypertensionaftercoronaryarterysurgery[J].ActaAnaesthesiolScand,2000,44(2):186-193.[11]LEVYJH,MANCAOMY,GITTERR,etal.Clevidipineeffectivelyandrapidlycontrolsbloodpressurepreoperativelyincardiacsurgerypatients:theresultsoftherandomized,placebocontrolledefficacystudyofclevidipineassessingitspreoperativeantihypertensiveeffectincardiacsurgery1[J].AnesthAnalg,2007,105(4):918-925.[12]SEGAWAD,SJQUISTPO,NORDLANDERM,etal.Cardiacinotropicvs.chronotropicselectivelyofisradipine,nifedipineandclevidipine,anewultrashortactingdihydropyridine[J].EurJPharmacol,1999,380(2-3):123-128.[13]ERICSSONH,FAKTC,HGLUNDL,etal.Pharmacokineticsandpharmacodynamicsofclevidipineinhealthyvolunteersafterintravenousinfusion[J].EurJClinPharmacol,1999,55(1):61-67.[14]SCHWIELERJH,ERICSSONH,LFDAHLP,etal.Circulatoryeffectsandpharmacologyofclevidipine,anovelultrashortactingandvascularselectivecalciumantagonist,inhypertensivehumans[J].JCardiovascPharmacol,1999,34(2):268-274.[15]BAILEYJM,LUW,LEVYJH,etal.Clevidipineinadultc