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VIENSOTRET KST CTTU BAOCAOKETQUANGHIENCIJUDCTAICAPVIEN NGHIENCLIUDANGBAOCHEVATIENLAMSANGCUATH UOCARTESUNATKETHOPVOIPIPERAQUINDELAMTH UOCCHLfASOTRET Chutridétcii •ThS TrinhN gocHai Coquanchutridétci i[.]
VIENSOTRET-KST-CTTU BAOCAOKETQUANGHIENCIJUDCTAICAPVIEN NGHIENCLIUDANGBAOCHEVATIENLAMSANGCUATH UOCARTESUNATK E T HOPVOIPIPERAQUINDELAMTH UOCCHLfASOTRET Chutridétcii.•ThS.TrinhN gocHai Coquanchutridét cii ’ V i é n sétr é t - KST - CTT U Ndm2006 VIENSOTRET-KST-CTTU BAOCAOKETQUANGHIENC’UUDETAICAPVIEN NGHIENCIIUDANGBAOCHE“VATIENLAMSANGCUATHU OCA R T E S U N A T KETH PVCIlPIP ERAQU IN DELAMTHUOCCHLfASOTRET Chitt r i d é tai:Th S Tr[nhN gocH a i CoquanchittrideHi:Viénsuitrét-KST-CTTU C:ipquénIQ:Viénsétrét-KST-CTTU M:iséidétai(néuco): Thiiigianthirchién:T’u:thang1ntim2005dé nthang12mhm2005 N%m2006 BAOCAOKETQUANGHIE“ NNCf fUDE NGHIENCL/U DANGBAOCHEVATIENLAMSANGCUATHUOCA R T E S U N A T KETHOPVIIPIPERAQUIN DELAMTHUOCCHLf ASOTRET ChutridéHi:TfiS.TrinhNgocHeir Paq u a n c h fit r i de Hi:Viéns i t rétKSTCTT O Coquanqu:inlydétai:ViénscotrétKST- CTTUDanhs:ich nhfmgngiioithirchiénchinh: - ThS.TrinhNgocH t i i - TS.NéngT h[ Tié n - DS.NguyénTh[Niéu - BS.N géV i é t Thiinh • BS.DoManhHit -KTV.DinhT h [ Yuan -PGS.TS.De›Hii:uNghi -T h S N guyénVénHén Thiiigia nt h i r c h i ( n : Titthang1mini2005dénth‹ing12niim2005 NHfJNGCHUVIETTAT ASAU Artesunat CDMS AreaUnderConcentrationDimethylsulfoxid ODHG Daihoc MPGS GoodManufacturePracticeGifios HCHP u LCICK Hfi ngcau ST HighPerformanceLiquidChromatographyInhibit KST- Concentration CTTUN Kysinhtriing PPCS Kysinhtritng-CfintriingTrunguong R Ngay PGS.TS.TLC Plasmodium PhongchongsotrétPhfigif UVW iosu,tiénst HO ThinL a y e r C h r o m a t o g r a p h y Trunguong Ultraviolet WorldHealthOrganization Nfiidung Trang » 2.TONGQUANDETAI: 2.1 TINHHINHNGHIENCIIUNGOAINU©C 2.2 TINHHINHNGHIENC N TRONGNU©C 3.DOTRONGVAPH1J©NGPHAPNGHIENCIJU: 11 3.1.NGHIENCNDANGBAOCHE 11 3.1.1 Ho:ich:i t,thiétbj 11 3.1.1.1 Hoachit 11 3.1.1.2 Thiétbi 12 3.1.2 Phuongph:ipnghiénemu 12 3.1.2.1 Bénlonghopatie›unat 12 3.1.2.2 Béochéviénnénphoihopai‘tesunatvapipei‘aquin 13 3.1.2.3.Phvongphcnd‹aiili giéchatlvongvién 14 3.2 NGHIENCIJUTACDUNGCUATHUOC KYSINHTRUNGSOTITINVIVOVAINVITRO 15 3.2.1 Nguyénliéu 15 3.2.1.1.Thuc›c 15 3.2.1.2 Kysinhtriingsoti‘éi 15 3.2.1.3 Siicvétthu:cnghiém 15 3.2.1.4 fleetchét 15 3.2.1.5.Dungcayte‘’vadungcuchuyéndung 16 3.2.2 Kythuatsirdungtrongnghiénemu 16 3.2.2.1 Phuongphcipinvitio 16 3.2.2.2 Phuongphé pinvi’vo 17 3.2.3.Chisod:inhgid 17 3.3 18 PHUONGPHAPXULYSOLIEU 4.KETQUANGHIENC L/U 19 4.l 19 NGHIENC NDANGBAOCHE 4.1.1 C‹ingthiiccho1viénthuiic 19 4.1.2 Khoilvongdongdenciiavién 20 4.1.3.Docling 20 4.1.4 Dinhtinh 20 4.1.5 D)nhluonghamlirongartesunatvépiperaquin 23 4.2 NGHIENCNTACDUNGDOIVII KYSINHTRUNGSOTITINVIVOVAINVITRO 23 4.2.1 T:i cdungdoiv‹iikjsinhtriingsiitréttrénnu‹iic:iy 23 4.2.2.Tticdungdoiv‹ii kjsinhtriing siitrétt r é n s i t e v:it thircn g h i ( m 24 BANL U A N 27 KETLUANVAKIENNGH! TAILIEUTHAMKHAO Thuocc o edur i o t p e r o x i d ( a r t e m i s i n i n v a d a n c h a t ) cotaed u n g h o t toankha cv6ic:iethuocsGtréthie:nd a n g co,lamottrong nhfmgqua nID hangd6ukhfi ngchiriengcuaVietNammaconcuan h i é u niioctrenth eg i c i i Tro ngailérnnhfitdfiivéithuoccocaun6iperoxidlatyletiiiphiitcao (10809«),malydocotheladothéig i a n banth a i n ga n dandengiamnhanhnongd otrongmii u,lamthuocnhanhhéttécdung.De:tanghieuquéd i é u trivagiémt yletaiphat,nhiéuc o n g trinhnghién c iiu dadnaranhtmgph:icdoke‘lhopkh:icn hau Viéckéthppgiiiac:ie thuoccocaunoiperoxidv6imotthuockh:iccothoigianbanthiidaihondelamtan ghie‘uquachfrabenhvagiémtylc:t:iiphat.Mfi tstcongtrinhdanghienciiutaora motsothuockethopnhuC V , a r t e k i n nhimgvanconmotsonhuncdiemnhu: vanco tiicdungphu(CV8),hoaccothedephMhuydodihydrroartemisinin(a rt e k in ) Hi ennayartesunatdangdvocsitdungrongr5itaiViétNamv i g i a thanhre,dfi bénvfmgcaohons o véic :ie danchatkhiic.N g h i é n c t i u ke t h o p artes una tv a piperaquin nhamt a o r a m o t d a n g t h u o c c h o n g t : i i p h a t , d e b é o q u é n v a s i r dung, g i a thanht h p l a d i é u r a t c a n t h i é t c h o c h i e n l i i o c s i r d u n g t h u o c s o t r é t c i i a ChuongtrinhQuocgiaPCSR Motsoccscrdasanxu6t thuocsotre’tvadong gopvematkhoahocchoChuongtrinhQuocgiaphongchongsotrét.Vi(nSotrétKST-CTTUcokhéuanghopt:ievéritruéingDaihocDuoc,notco 'nccsosituxuatdattiéuchua nGMP(doDit:inPCSRVi(tUcHitrcrtruocday)desénxu6tthuocsotrétm6icohi(o quécao.D6yclinglanghie‘ncirumodaudecosoli(ugiiipchoviecxinkinhphicacnghié ncilritic:ptheosédunekethppv6itruéngDH GorthenborgT hu y Die‘n MUCTIEUNGHIENCN Nghic:nciiudangbaochc:artesunatkéthppvoipiperaquin(arteraquin) X:icd)nhtiredungciiathuocdoivéi invitrova kys i n h t r i i n g s i t r e’t ‹ evivotrénsiicv4tthucnghi(m » 2.TONGQ U A N D E TAI 2.1 TINHHINHNGHIENCtlUNGOAINU6C: Tirnam1 cacnhakhoahocTrungQuocbatdannghic:nciluvethu occocauriotperoxid( a r t e m i s i n i n va danch:it).Chode"nnayartemisi nin,artes una t daquacacbuiicnghié n c i lu ciiamotthuocsotrétdoWHO quidinhvada duocsén xuatt a i TrungQuocva mots o nucrctrongdfi co Vi(tNam.Tha ng 9/ 19 93 WHOda tochucHfiinghit u van”Artemisininv adanchat”LaiGeneved5nhanmanhdenyéucandambaochdtlirong,quanlychatche vasirdungantoandoivi5iartemisininvadanchat Piperaquind u o c RhoneP o u l e n c t o n g hpptit nhfmgna m va motth6pkysaudfida duocVténNghiénciiuCongnghi(pDuocThuongHii,T r u n g Q u o c s i r dun g.N o t h a y t h é c h o c hloroquin n h i i lat h u o c s i t dungcho tuyénd dut r o n g n h i é u v i i ngo TrungQ u o c t r o n g n h tmnam1970va1980.Ngoairamot sonhfikhoahocTrungQuoccondnaradangthuock é t h p p g i i i a p i p e r a q u i n v a a r t e m i s I n i n ( 0 m g + m g ) g o t l a artequick,cohi(uliic tfitv6ikysinhtriingsotrét.TrongthciigianchongMythaocsotrétdachieucu a TrungQuocdiingchobodfiiVi(tNamla ViénphongIII,trongdficokéthppchu yéuv6ipiperaquin Conhie‘unghiénelmve'cécph:iedfike"thopgifrathuoccocaunoiperoxid vé ri tha0cs o t rétkhac.TaiThaiLa ndake"ihppthuocartesunat v6imeflo quinth6ycohi(uquacaovoiKSTsotre’t,tyl(I:iiph:it thap TaiT r u n g Q u o c , G S L e e d f i t h i i n g h i e‘mt a i n s a n g v i e n C V v a artekintaiVi(tNam.Kétquachothayhaithuockéthpp naycotacdungtotv6ikysinhtriingsotrét 2.2 TINHHINHNGHIENCIIUTRONGNU©C: Thuoccoc6unoiperoxiddaduocnghiénctirititnam1 ciVi(lNam ,thuocdaducicthit nghiéminvitrovainvivotaiVie‘nSotre’t-KST- CTTI.I,kitquachothdyartemisinintothon4-5lansov6imefloquin,2830l6nsovéiic h l o r o q u i n va lansovciiquinin( N g u y ‹ : n D u y Sy va co ngsu,1992) Hauhétcactiicgiénghienc iiudenconh"anxétchungladiilieuthapvoitong1 i‹:u lal g haylieucao5gthiartemisinindc : u catso1vasachKSTtruoc48gi osaukhiufi ng thuoc(NgoyénDuySyvacongsu,1992).C h o denna y d i é u t r i s o t r é t a c ti nhc h i n y é u d n a vaoca c thuocs o t ré t tiém,truyénnhuquinin,artesunat ,die anaykhfi ng thudntien otuyenccs o Mfitsonghiénelmchothayvoiartesunattiémbapthitlieu240mgJ3ngay, 360mg/5ngay,480mg/ 7ngay,kétquatyI(HiphatgiimdantheoThutLf529n,109ova39o(NguyenDuy Sy, 1995) Artesunatdangviendvocs i r d u n g c h i t y é u ded i é u t r i sotr é P.falcipai‘umk h an g t h u o c N h i é u d a n c h i t k h a c c i i a a r l e m i s i n i n c l i n g dangduocnghic:nciluvathitnghie‘mlamsangtaiVi(tNam Hi(nnaydohanchéciiaartemisininvaariesunatvetyI(Laiph:itcaosaudieut r i néncacnhanghiénc i i u dangcogangtimranhfmgdinchitcokhénangk hacphucdirocvande nay.Hu6ngnghi6nciiuchinyentiptrungkéodaithéigianbénthaiciiathuoc de"nongdothuocduytritrong in:iulauhon.Dieunayconghiacmkethppchiingv éimot thuocsotre’tco théigianb:inthiidaihon Nghiénelmgind:Iydaphoihppdihydroartemisininvoipiperaquin,prim aquin,trimethoprim(viénCV8)doVi(tnamsénxuatchothaycotiredungc h o n g I : i i p h : i t , n h u r i g v a n c o t:ied u n g p h u n h u : b u f i n n f i n,d a u bung (MichaelAshton,TrinhNgpcHai,2003J Vi(nSotrétkéthppvoimob soccrs‹s é n xuatdathirnghiémthuoc Arterakin( h o n h p p t h u o c k e t hp pg i f i a d i h y d r o a r t e m i s i n i n 40mgv a piperaqain320mg),cohi(u luccaovoikysinhtrilngsotrétvasitdungantoan.Phacdhsirdungcuaarterakinla2 viensau0,8,24va36gio.Tonglieul a 8vién Trongdc:tdinay,TruongdaihocDuocHaNfiivdVi(:nS0trét-KSTCTTUnghienctiudangthuocke“thppgiiiapiperaquinv a thuoccfihieul vc caov6iKSTsotrét,ddylahittingnghiénc iiumcritimrathuficsfitrét cohieuluccao,chong Laiphét,giathanhthdpvaantoan chonguéisirdung 3.3.PHUONGPHAPX ULYSOLIEU - Sankhimayghicfiahe’thGngsaeky'longcaoapchobiétnongdfidu6idvéngcong(AUC )thichosolieuAUCvaobéngSparseDataAnalysisduoccaidatsantronghethong may tinhtabiét duocnongdficiiamaucando -ThongJ‹ésos:inhhieulucdieutn:diingT-test -Cacsolie‘unghienctruse‘dvocxirlybangphanmémEPI-Info6.0vaStata 6.0 18 4.KETQUANGHIENCLfU 4.1 NGHIENCUUDANGBAOCHE: 4.1.1 Cfingthficcho1viénthuoc:Artera quinI : Artesunat 50mg Piperaquin phosphat: 320mg6-cyclodextrin(hoactween80) 30mgPolyvinylp y r r o l i d o n 6mg Talc 6mg Magnesistearat 3mg Lactose+Tinhbotmi+Microcrystallinecellulose:viiadii600mg Arteraquin2: Artesunat Piperaquinphosphat:T alc Magnesis t e a r a t Eratab Microcrystallinecellulose Arterau i n 3: 50mg 320mg vd vd vd vd Artesunat; 50mg Piperaquinp h o s p h a t 320mg Doxycylin: 10mg 6-cyclodextrin(hoactween80) 30mgPolyvinylp y r r o l i d o n Talc Magnesistearat 6mg 6mg 3mg Lactose+Tinhbdtmi+Microcryslallinecellulose:viiadii600mg Arteraquin4 : Artesunat 40mg