ElutaxII
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Transcript of ElutaxII
DRUGELUTINGBALLOON
ELUTAX
Dr.med.AlexanderRuebben
DRUGELUTINGBALLOON
WHY?
Dr.med.AlexanderRuebben
UNSOLVEDDESPROBLEMS
• IN‐STENTRESTENOSIS• BIFURCATIONS• SMALLVESSELS
• DIABETES• ACUTEMI
NewEngJMed2006,355:2113‐24
ADVANTAGESOFTHENEWTECHNOLOGY
• ONESHOTDRUGAPPLICATION• NOTRIGGERTOFOREIGNBODYREACTIONDUETOSTENT
• NODISTORTIONOFORIGINALVESSEL„BIF“• NOINFLAMATIONDUETOPOLYMER
• NOMULTIBLESTENTLAYERSINBIFURCATIONSORIN‐STENTRESTENOSIS
Hwang, Circulation 2001; 104: 600-5
Homogenous Drug transfer!
PaclitaxeldeliverythroughDESVERSUSDEB
SchellerPaccocath
Effects of Paclitaxel
After dilatation we have maximum drug dose at the
vessel wall, which can be measured for min. 2 days.
However the Drug action persist for at least 2 weeks
Axel, D. I. et al. Circulation 1997;96:636-645
Copyright ©1997 American Heart Association
Axel, D. I. et al. Circulation 1997;96:636-645
Immunofluorescence micrographs demonstrating the effect of 1.0 micromol/L paclitaxel on the distribution of the contractile filament smooth muscle {alpha}-actin and the intermediate filament vimentin in haSMCs
Axel, D. I. et al. Circulation 1997;96:636-645
Immunofluorescence micrographs showing the effect of 1.0micromol/L paclitaxel on cytoplasmic microtubule distribution
Disrub[onofmicrotubuli
LESSONSLEARNEDTILLTODAYPUREPACLITAXELWITHOUTANYMATRIXOR
ADDITIVEISNOTOPTIMAL!
CremersDGK2008
However‐Dior1genera[on:StellaPCR09
WHICHTECHNIQUEISUSEDTODAYtoFreePaclitaxelandtoensureUp‐take
• MixtureofPaclitaxelwithHydrophilicandLipophilicAddi[ve:
• SequentPlease‐BBraun• In.PactAmphirion‐Invatec
• MixtureofPaclitaxelandShelacsolu[on• DIOR(2ndGen)‐Eurocor
• MatrixofpurePaclitaxel„Ice“and„Snow“• ELUTAX–AachenResonance
Whatdoesthismean?
• Amixtureofdifferentcompoundswithpaclitaxelguaranteesadiffusionfromtheballoonandanuptakeintothevessel
DrawBack!!!!
• Thereleasebeginnsoncethecatheterisincontactwithfluids!!!!!!!!
• Theamountofdruguptakedependsonthedura[onoftheprocedure!
ELUTAX
• Homogenouscoa8ng
• EvenandConsistentcoa8ngofinflatedBalloons• DrugMatrixofpurePaclitaxel(twolayersSNOWandICE)
• Balloonwith360Degreecoa8ngcoverage• MinimalDruglostduringpassageinthebody
• MinimalDruglostfromtheballoonsurfaceduringmaneuverorinfla8on
• Reliablequan8ta8veDrugdeposi8onintothevesselwall• SafeDrugTransfer• Noaddi8onalsubstances• NoCracks
WhichDrugdose?2or3microgramm/mm2
WhatmaSersisnotthedrugdoseontheballoonbuttheDrugwhicharrivestothevesselwall!!!!
12h 0,19 9,80 7.79 8,08 0,74
proximalreference
proximaldilatedsequence
distalreference
middledilatedsequence
distaldilatedsequence
1 2 3 4 5
1 2 3 4 5µmol/l
Arterial[ssuepaclitaxelconcentra[onamerELUTAXballoondilata[on
1h 6.9 58,7 66,2 79,2 7.0.
proximalreference
proximaldilatedsequence
distalreference
middledilatedsequence
distaldilatedsequence
1 2 3 4 5
1 2 3 4 5 µmol/l
ELUTAX
Gyöngyösi
Pharmacokinetics of ELUTAX
1min60min12hours
Dior1gen.
Elutax2ndgen.
0
50
100
150
200
250
1 2 3 4 5
Foratleast12hourswehaveatherapeu[cdoseinthevesselwall!
Gyöngyösi
([ssueconcentra[onofpaclitaxeleffec[vefrom56nMto50µM,toxiceffectover100µMincellculture,Axeletal.Circula.on1997)
Gyöngyösi
StellaPCR09
Productswithtoxic[ssuePaclitaxelconcentra[onlongerthanonehour
SequentPlease
Diorcurrentcoa[ng
([ssueconcentra[onofpaclitaxeleffec[vefrom56nMto50µM,toxiceffectover100µMincellculture,Axeletal.Circula.on1997)
SequentPlease
EurocorDIORnewcoa[ng
WhichProblemscanoccur,iftootoxicDrug‐levelsareapplied:?
Differentaspects:Coa[ngtechnique
• EUROCOR,INVATECandBBraun,arecoa[ngafoldedBalloon!
• AACHENRESONANCEcoatstheinflatedballoon
Seethedifference
Exampleforunevencoa[ng:NewDIORBALLOON
Totallyunevenwithbigcrystals,nearlynoPaclitaxelinFolds
OpeningBehaviorofDifferentBalloons:
ELUTAX
Mul[pleDrugDebrisarefallingoftheBalloonduringInfla[on!
Mul[pleDrugDebrisarefallingoftheBalloonduringInfla[on!
ELUTAX
NODrugDebrisarefallingoftheBalloonduringInfla[on!
Results
Mul8pleDrugdebrisarelostduring
Infla8on
Mul8pleDrugdebrisarelostduring
Infla8onNODruglost!
MinimalDrugcontentoninflatedBalloon
Onlypar[aldrugloadremainsonthe
Balloon
Fullyloadedballoonreachesthevessel
wall
Drugdebrismaybedangerouscausingdistalembolism
Drugdebrismaybedangerouscausingdistalembolism
SAFE!
UNIVERSITÄTSKLINIKUM DES SAARLANDES
NewFron[ers:renalarteryTreatmentofIn‐stentRestenosiswithELUTAX
Prof.Reul,BetaKlinik,Bonn
NewIndica[ons
5MonthAngioandMRFollow‐up
NosignofRestenosis!
Dialysis Patient
42 years
UNIVERSITÄTSKLINIKUM DES SAARLANDES
NewIndica[ons
IasisCE‐trial(Bulgaria)In‐Stentrestenosis,withangiographicfollow‐up
amer6months:
performedbyDr.IvanManukov,HeadofDepartmentIntervenDonalCardiology,UMBALSveDGeorgiHospital,Plovdiv,
Bulgaria
43pa[entstreatedwithElutax0%restenosis