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Átírás

1 Ml1H3ilPAB POCCMH Cf-oos;ti/og _ cor ~~ o BA HO z 6 o MHHHCTEPCTBO 3.[(PABOOXPAHEHHJI POCCHHCKOH <I>E.[(EPAUHH HHCTPYKUHJI no ME.[(HUHHCKOMY nphmehehhio JlEKAPCTBEHHOfO npenapata PentcTpauuounbtil nomep: JlCP /08 Toprosoe naumenosanue npenapata: TonaMaKc Meii\Aynapo,nnoe nenateiitobannoe nanmenosanue: TOm1paMaT JletmpcTBennaH «J-opMa: Kancyllbl CocTaB.[(eHCTBYIOW.ee BeW.eCTBO: TOnHpaMaT 50 Mr. BcnoMoraTellbHble Bew.ecTBa: caxapha.r KpynKa [caxap03a, natoka KpaxMaJlbHa.R] 150,00 Mr, nobh,ij,oh 34,733 Mr, L(elllll01l03bl al(etat 18,076 Mr. CocTaB TBep,!J,OH jkellathhoboh Kancyllbi: j((ejlathh 80,6-83,5 Mr, BO,IJ,a 12,5-15,4 Mr, cop6htaha 11aypaT 0,0397 Mf, HaTpii.R JlaypHllCYllbcpaT 0,0397 Mf, HITaHa,IJ,HOKCH,IJ, (E171) 0,99 Mf, 4epHHJla Opacode Black S /23 YepHbie ( coctab YepHHll: pactbop r11a3yp11 we1111aka B :nahojle, jkelle3a OKCH,IJ, 4epHbiH, H-OYTHJlOBbiH cn 11pT, 1130nponHllOBbiH CnHpT, npomfjlehrllhkojlb, ammohh.r fh,!j,pokch,ij,) 5-10 MKf. Onucanne Kancyllbt 50 Mr: TBep,!J,ble j((ejlathhobbte Kancyllbl N!! 0, cocto.rw.ue H3 Kopnyca 6e11oro ~..(BeTa H npo3paljhoh 6ecl(BeTHOH KpbiWe4KH. Ha KpbiWeLJKe Kancyllbl HMeeTc.R Ha,IJ,nHcb LJepHbiMH 4epHHJlaMH "TOP". Ha Kopnyce Kancyllbl HMeeTc.R Ha,IJ,nHcb LJepHbiMH LJepHHJlaMH "50 mg". Co,!J,epj((HMoe Kancyll - rpahyllbl 6e11oro noljnt 6e11oro ~..(BeTa. <l>apmakotepanebtii'ieckah rpynna: nponib03mtllenth4eckoe cpe,!j,ctbo. Ko,n A TX: N03AX 1 1 <l>apmakonont'lectme csoilctba ([Jap.ltaT-:odztHa\lu~-:a TonupaMaT.RBJl.ReTc.R nponibo3nhllenthljeckiim npenapatom, OTHOC.RW.l1MC.R K KJlaccy cyllbcpamat- 3aMew.eHHbiX MOHOCaxapH,!J,OB. TonupaMaT 6JlOKHpyeT HaTpHeBbte KaHaJlbl 11 no,ij,abjl.ret B03HHKHOBeHHe nobtophbix notehl(hajlob,ij,ehctbh.r Ha cpohe,ij,jlhtellbhoh,ij,enoll.rph3al(iih MeM6paHbl Hei1poHa. TonupaMaT nobbiwaet akthbhoctb y-amhhomacjl.rhoh KHCllOTbl (f AMK) B OTHoweHIIH HeKoTopbiX no,ij,thnob ramk-pel(emopob (B TOM LHJCJle ramka-pel(emopob), a TaiOI<e MO,IJ,ymtpyeT akthbhoctb CaMHX r AMKA-pel(emopOB, npen.rtctbyet akthbal(hh Ka~JHaTOM LIYBCTBHTellbHOCTH no,ij,ntna KaiiHaT/ A MnK (a-am HH0-3-rH,!J,pOKCH-5-MeTHllH30KCa3oll-4-npomtoHoBa.R KHCllOTa)-pel(emopoB K rllytamaty, He BllH.ReT Ha akthbhoctb N-MeHIJl-0-acnapTaTa (NMDA) B OTHOWeHHH no,ij,tlma

2 NMDA-peuemopos. 3TH 3cpcpeKTbl TonHpaMaTa HBJHJJOTCH.U03o3asucHMbiMH np11 KOHUeHTpau~lll npenapata B nj1a3me OT I MKMOJlb,[1,0 200 MKMOJlb, C MIIHHMaJlbHOH akthbhoctbio B npe.uenax OT I MKMOJlb,[1,0 I 0 MKMOJlb. KpoMe Toro, TOnHpaMaT yrhetaet akti1bhoctb HeKOTOpblX mocj>epmehtob Kap6oaHm.upa3bl. no Bblpa)l(eHHOCTH 3TOrO cpapmakojlorj.jlieckoro 3cpcpeKTa TOnHpaMaT 3HalfHTeJ1bHO ycrynaet aueta30j1amh.uy - H3BeCTHOMY 11HrHOHTOpy yrojlbhoh ahrh,upa3bl, n03tomy 3Ta aktiibhoctb TOnHpaMaTa He ClfHTaeTCH OCHOBHbiM KOMnOHeHTOM ero npothb03nhnenthlfeckoh aktiibhocth. cfjap.licikoi-.."l/1/e/111/1-.."c/ TonupaMaT BCaCbJBaeTCH ObiCTpo H 3Cpcj>eKTHBHO. Ero 6uo.uocTynHOCTb COCTaBJlHeT 81%. npuem niiluh He OKa3biBaeT KJlHHHlfeCKH 3HalfHMOrO,UeHCTBWI Ha OHO,[I,OCTynHOCTb TOnHpaMaTa. C 6eJ1KaMH nj1a3mbl CBH3biBaeTCH 13-17% TOnHpaMaTa. nocne O,[I,HOKpaTHOrO nphema B,[1,03e,[1, Mr cpe,d.hhh OObeM pacnpe.uenehhh coctasnhet 0,55-0,8 nikr. BenHlfHHa o6bema pacnpe.uenehhh 3aBHCHT OT nona: y )KeHW.HH OH COCTaBJlHeT nphmepho 50% OT 3HalfeHHH, HaOJliO,UaeMbiX y MY)I(lfHH, '-ITO CBH3biBaiOT C 6onee BbiCOKHM CO,Uep)l(aHHeM )I(HpOBOH TKaHH B oprahh3me )l(ehw.hh. nocne nphema BHYTPb MeTa60J1H311pyeTCH OKOJlO 20% OT nphhhtoh,[1,03bl. O;D,HaKO y OOJlbHbiX, nonyyajow.hx conytctbyjow.yio TepanHJO nponjb03nunennjyeck11mh npenapatamh, KOTOpble IIH.UYUHPYIOT cpepmehtbl, OTBelfaJOW.He 3a MeTaOOJ1113M JleKapCTBeHHbiX cpe,uctb, MeTaOOJ1113M TonHpaMaTa nobbjwaetch.uo 50%. lth nna3mbl, M0' cpekani1h YenoseKa 6bJJ111 BbJ.UeneHbl 11 u.uehthcphuiiposahbl wectb npakthlfeckh HeaKTIIBHbiX MeTa6omJTOB. OcHOBHbiM nytem BbJBe.UeHHH HeH3MeHeHHoro TonupaMaTa (70%) 11 ero MeTa6omJToB HBJlHJOTCH nolfkh. nocne nepopanbhoro BBe,UeHHH nna3mehhbih KJlHpeHC nmupamata COCTaBJlHeT MJlfMHH. <l>apmakokhhethka TOnHpaMaTa HOCHT JliiHeHHbiH xapaktep, nna3mehhbih KJlHpeHC OCTaeTCH noctohhhbim, a njlow.a,ub no.u KpiiBOH «KOHUeHTpaUHH-BpeMH» (AUC) B,UHana30He,[1,03 OT 100,[1,0 400 Mr B03pacTaeT nponopuuohajlbho.uo3e. Y 6onhHbiX c HOpManbHOH cpyhkuuei1 nolfek.d.j1h.uoctjj)i(ehhh yctohlfhboh KOHUeHTpaUHH B nna3me MO)I(eT noha.uoohtbch OT 4,[1,0 8,[I,HeH. 8eJllllfHHa MaKCHMaJlbHOH KOHUeHTpauuu (Cmax) nocne MHoroKpaTHoro nepopanbhoro np11ema I 00 Mr npenapata.usa)l(.[l.hi B.ueHb B cpe,uhem COCTaBI1Jla 6, 76 MKr/MJl. nocne 1\fHOrOKpaTHOrO nphema,[1,03 no Mr,[I,Ba)l(,[l,bl B,UeHb nepuo.u nonybhjbe.uehhh TOmlpaMaTa 113 nna3mbl B cpe.uhem coctabhjl 21 Yac. Y 6onbHbiX c HapyweHHHMH cj>yhkuihi noyek cpe.uheh 11 TH)I(enoi1 ctenehh nnajmehhbih 11 noyelfhbih KJ111peHC TOmlpaMaTa CHH)I(aeTCH (KnHpeHC KpeaTHHI1Ha (KK) :S 70 MJl/MHH), KaK CJle,UCTBHe B03MQ)KHO nobbjwehhe pabhobechoh KOHUeHTpaUIHJ TOnHpaMaTa B nna3me KpOBH no cpabhehi110 C nauhehtamh, IIMeJOW.HMH HOpManbHYJO cpyhkuhjo nolfek. KpoMe Toro, nauuehtam c HapyweHIIHMH cj>yhkuhh nol.fek Tpe6yeTcH 6onbwe spemehij.unh.uocti1)1(ehiui pashosechoil KOHUeHTpauHI1 TonupaMaTa s KpOBII. nauhehtam CO cpe,uheh IIJlll TH)KeJlOH noljelfhoij He,UOCTaTOlfHOCTbiO pekomeh,uyetch nphmeheh!je nojlobhhbl pekomeh,uobahhoh HaLJaJlbHOH H no.u.uep)i(hbajow.eh,[1,03bl. TonupaMaT 3cpcpeKTIIBHO BbiBO.UHTCH 113 nna3mbl nytem remo.uhaj1h3a.,umnenbhbih remo.uuanu3 MmKeT nphbectii K CHH)I(eHHIO KOHUeHTpaUIIH TOnHpaMaTa B KpOBH HmKe KOJ111lfeCTBa, Tpe6yJOW.erOCH.D.J1H no.u.uep)l(ahiih npon1bocy.uopo)i(hoh aktiibhocth. Bo 1136e)l(aHue 6b1CTporo na.uehhh KOHUeHTpaUHH TOnllpaMaTa B nj1a3me BO BpeMH remo,uiiaj1h3a, MO)I(eT notpe6osatbch Ha3HalfeHHe.uonomnJTeJlbHOH,[1,03bl npenapata TonaMaKc. npu KOppeKUHH,[1,03bl cne.uyet npllhhmatb BO BHIIMaHHe: I) npo.uon)i(htejlbhoctb remo.uhamj3a, 2) BeJllllfiiHY KJlHpeHca IICnOJ1b3yei\10H CIICTeMbl remo,[i,haj1113a, 3) 3cpcj>eKniBHbiH nolfelfhbih KJliipeHc TonupaMaTa y nauuehta, Haxo.uHw.erocH Ha.UHaJ1H3e. 2

3 nml3mehhbih KJlHpeHC TOnHpaMaTa CHH)J<aeTC.II B cpenhem Ha 26% y nauuehtob C neyeh04hoh HeJlOCTaT04HOCTbiO cpenheh HJ111 T.II)KeJlOH CTeneHH. no3tomy nauhehtam C neyeh04hoh HeJlOCTaT04HOCTbiO CJleJlyeT nphmeh.htb TOnHpaMaT C OCTOpO)KHOCTbiO. Y no)khjlbix nauuehtob 6e3 3a6onesaHui1 noyek, nna3mehhbih K!l11peHc TonupaMaTa He MeH.sJeTC». f{jap.hcikok'llllemuka monupa.hama y ijemeit ijo 12 J7em cl>apmakokliheth4ecki1e napametpbl TOn11paMaTa y jleteh, TaK )Ke, KaK y B3pOCJlbiX, nojlyyaiow,hx 3TOT npenapat B KaYeCTBe BCnOMOraTeJlbHOH Tepamm, HOC.IIT JlHHeHHbiH xapaktep, np11 3TOM ero KJlHpeHC He 3aBHCHT OT Jl03bl, a pabhobechble KOHUeHTpaU1111 B njla3me B03pacTaiOT nponopuhohajlbho nobbjwehhio Jl03bl. CnenyeT yyhtbjbatb, onhako, TOT cpakt, YTO y neteh K!lllpeHc TOn11paMaTa nobbjweh, a nep11on ero nonybbjbenehjui 6onee KopoTKHH. CnenosaTeJlbHO, np11 OJlHOH H TOH )Ke Jl03e, B pacyete Ha l Kr MaCChi TeJla, KOHUeHTpaUlnl TOnHpaMaTa B njla3me y JleTeH MOryT 6b1Tb HH)Ke, YeM y B3pOCJlbiX. Y JleTeH, KaK H y B3pOCJlbiX, npothb03m1jlenth4eckhe npenapatbl, HHJlYUHPYIOW,He M~lKpOCOMaJlbHble cpepmehtbl neyehh, Bbl3b1BaiOT CHH)KeHHe KOHUeHTpaU11H TOnHpaMaTa B njla3me. llok333hiih K DpHMeHeHIIIO.. 3mL'le IIC UR 8 KaYeCTBe cpejlctba MOHOTepamm: y B3pOCJlbiX H JleTeH CTapwe 2-X JleT C 3m1JlencHeH (B TOM 411CJle y nauhehtob C BnepBble nuarhocnjposahhoh 3nHnencuei1). 8 COCTaBe KOMnJleKCHOH TepanHH: y B3pOCJlbiX 11 JleTeH CTapwe 2-~ JleT C napuiiajlbhbimh HJlH rehepa!lh30bahhbimi1 TOHHKO KJlOHI14eCKHMH nplmankamh, a TaK)Ke JlJl» neyehllil npunankob Ha cpohe CHHJlpOMa JleHHOKca-racmo. Mtupellb npocpi!jlakthka nphctynob MHrpeHH y nphctynob MllrpeHH He 113y4eHO. B3pOCJlbiX. npumehehj1e TonaMaKca JlJl.ll JleYeHH.II OCTpbiX flpothbodok333hiih nobbjwehha.ll YYBCTBHTeJlbHOCTb K JliOOOMY 113 KOMnOHeHTOB.D.aHHOrO npenapata.,lj;etckiih B03paCT X JleT. npl!mehehhe TOnHpaMaTa JlJl.ll npotjnjjlakthkh nphctynob MHrpeHH npothbonoka3aho B nepho.ll. 6epeMeHHOCTH, a TaK)Ke y )KeHW,HH C COXpaHeHHbiM.D.eTOpO.ll.HbiM notehuliajlom, He IICnOJlb3YIOW.IIX Ha.lJ.e)KHble MeTO.ll.bl KOHTpauenUHH.,lJ;ecpllUHT caxapa3blfi130majlbta3bl, HenepeHOCHMOCTb cppykt03bl, rjliok030-ranakt03hu.ii Manba6cop6UH.II. llpnmeuenne npu 6epeMenuocTn 11 B nepno.lj. rpy.lj.noro ockapmjjiibaijuh TonupaMaT npo.iibjl.iijl TepaToreHHble CBOJlcTBa y MbJWeH, KpblC 11 Kp0Jli1KOB. Y KpblC TOnHpaMaT n pomjkan Yepe3 nnauehtaphbih 6apbep. CneuuanbHbiX KOHTponupyeMbiX ljccne.uosahhh, B KOTOpbiX TonaMaKc nphmeh.sjjlc.ii 6bJ.ll.Jl.ll neyehi epemehhbjx )KeHW,HH, ue npobo.ll.hjlocb. TonHpaMaT MO)KeT nphyhhhtb spe.u nno.uy np11 np11mehehi1h Y 6epeMeHHbiX ikehw,hh. JJ:aHHble yljeta 6epeMeHHOCTeH CBI1.D.eTeJlbCTBYIOT, 4TO y MJla.D.eHUeB, no.usepraswuxc.11 B03.D.eikTBHIO TonupaMaTa rmympuympo6uo B TeYeHJJe nepsoro TpHMecTpa 6epeMeHHOCTII, IJMeeTC.II nobbjwehhbih pi!ck pa3bhth.ii BpO)K.lJ.eHHbiX nopokob pa3bhtiui (Hanp11Mep, 3

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5 (HanpHMep, )J.eTH H nmkhjlble nauuehtbl). KancyJlbl TonaMaKc cjle)j.yet octopmkho OTKpblTb, cmewatb co)j.ep)i(hmoe KancyJl c He60JlbWHM KOJlWleCTBOM (OKOJlO I 4aHHOH JlO)I(KH) KaKOH-JlH60 M.HrKOH nhw,h. 3Ty CMeCb CJle)J.yeT HeMe)J.JleHHO nporjlothtb, He pa3)kebbiba.h. He CJle)J.yeT xpahhtb JleKapcTBeHHblH npenapat, cmewahhbih c nuw,ei1, )J.O cjlejl.yiow,ero npuema. KancyJlbl TonaMaKc MO)I(HO nporjlatbjbatb uejlhkom. IIapuuaJibHbte unu reuepanujooauuble TOHUKO KJIOHifltectme npuna~ku, a TaK:.Ke nptma~ku ua cijone CIIH~pOMa JleHHOKCa-racTO /7pzweHeHlte 8 KO.ll6UHGlfUll C opy2umll np0111ll80cyoopo:jichbl.llll npenapamalllt y 83pOC.'lblX 11GlflleHJ1108 MHHHMaJlbHa.H 3cp<j>eKTIIBHa.H )J.03a COCTaBJl.HeT 200 Mr B )J.eHb. 06bJ4HO CYMMapHa.H CYT04Ha.H )J.0'3a coctabjl.het OT 200 Mr )J.O 400 Mr 11 nphhhmaetc.h B )J.Ba nphema. HeKoTopblM 6oJlbHbiM MO)I(eT noha)j.o6htbc.h ysemj4ehhe cyt04hoh )J.03bl )J.O MaKCHMaJlbHOH - I600 Mr. PeKoMeH)J.yeTC.H Ha4aTb Jle4eHHe C HH3KOH )J.03bl C nocjle)j.yiow,hm noctenehhbim no)j.60pom 3cpcpeKTHBHOH )J.03bl. 0o)J.60p )J.03bl Ha4HHaiOT c Mr, nphhhma.h ux Ha H04b B Te4eHJJe I He)J.eJlH. B )J.aJlbHei1weM c He)J.eJlbHbJMH HJlH Jl.BYXHe)J.eJlbHbiMH HHTepBMaMH )J.03Y MO)I(HO ysejll14hbatb Ha Mr II nphhhmatb ee B )J.Ba npuema. Op11 no)j.6ope )J.03bl Heo6xo)J.HMO pykobo)j.ctbobatbc.h KJlJJHH4eCKHM J<j>cpeKTOM. Y HeKOTOpblX 6oJlbHbJX 3<j>cpeKT MO)I(eT 6b1Tb )J.OCTHrHyT nph nplleme npenapata I pa3 B cytkh..[(jl.h )J.OCTH)f(eHH.H onthmajlbhoro J<j><j>eKTa Jle4eHH.H npenapatom TonaMaKc He o6.h3atejlbho KOHTpOJlHposaTb ero KOHUeHTpaumo B njla3me..lj:ahhble pekomeh)j.auhh no )J.03e nphmehhmbl KO BCeM B3pOCJlbiM nauuehtam, BKJ1104a.H no)f(hjlbix Jl io)j.eh, nph OTCYTCTBHH y HHX 3a60Jl~BaHH.H no4ek (CM. pa3)j.ejl "0co6bJe yka3ahh.h"). Ko.lt6tm11p08QHHQJI npomueocyoopo;;jc1/qfl111epamm y oemeii cmapwe 2 Ile/11 PeKoMeH)J.yeMa.H cymmapha}! cyt04ha}! )J.03a npenapata TonaMaKc B Ka4eCTBe cpe)j.ctba )J.OnOJlHHTeJlbHOH TepanHH COCTaBJl}!eT OT 5 )1.0 9 Mr/Kr H nplihhmaetc$1 B )J.Ba nphema. 0o)J.60p )J.03bl He06XO)J.HMO Ha4aTb C 25 Mr (HJ111 MeHee, OCHOBbJBa.HCb Ha Ha4aJlbHOH )J.03e OT I )1.0 3 Mr/Kr B )J.eHb), nphhi1ma}! ux Ha H04b B Te4eHHe I He)J.eJlH. B )J.aJlbHeilweM c He)J.eJlbHbiMH HJlH Jl.ByxHe)J.eJlbHbiMH IIHTepBMaMH )J.03Y MO)I(HO ysemj4hbatb Ha I - 3 Mr/Kr II nphhjjmatb ee B )J.Ba nphema. 0pH no)j.6ope.'l03bl Heo6xO.llJJMO PYKOBO)J.CTBOBaTbC}! KJlliHll4eCKHM 3cpcpeKTOM. no)j.6op )J.03bl Ha4HHaiOT npenapatom TonaMaKc Kancynbl B )J.03HposKe IS Mr Mr. CyT04Ha.H )J.03a Jl.O 30 Mr/Kr o6bj4ho xopowo nepehochtc$1. 3nunencuu (B TOM 'IIICJie onepoble ~uaruoctupooauuau) lvfmwmepamm: oou{ue noiioj/cehufl 0pH OTMeHe conytctbyiow,hx npotiibocyjl.opo)i(hbix npenapatob C UeJlbiO MOHOTepamHJ TOnHpaMaTOM Heo6xo)J.HMO Y4HTbJBaTb B03MO)I(HOe BJlJJ}!HHe JToro wara Ha 4aCTOTY npuna)j.kob. B Tex cjly4a.hx, KOr)J.a HeT He06XO)J.HMOCTH pe3ko OTMeH.HTb conytctbyiow,he npotiibocyjl.opo)i(hble npenapatbl no C006pa)f(eHH$1M 6e3onaCHOCTI1, pekomeh)j.yetc$1 CHJJ)I(aTb IIX )J.03bl noctenehho, ymehbwa$1 )J.03Y conytctbyiow,hx npothb03njijlennj4eckhx npenapatob Ha O)J.Hy TpeTb Ka)I()J.ble 2 He)J.eJlH. Op11 OTMeHe npenapatob,.hbjl}!iolll,hxc$1 IIHJl.YKTOpaMH 1\HIKpOCOMaJlbHbiX cpepmehtob ne4ehh, 6y)J.yT B03pacTaTb KOHUeHTpaUHH TOnHpaMaTa B KpOBH. 8 TaKHX CI1TyaUI1$1X, np11 HaJlH4HH KJlHHI14eCKliX noka3ahhh )J.03Y npenapata TonaMaKc MmKHO chm~itb..\1ohomepamm: e3pocilble B Ha4ane ne4ehh$1 nauheht )J.OmKeH np11hhmatb no 25 Mr npenapata TonaMaKc nepe)j. CHOM s 5

6 Te4eHI1e I He.IJ.enl1. 3aTeM.IJ.03Y nobhiwaiot c 11HTepsanoM s I - 2 He.IJ.emi Ha Mr (cyt04hyio.ij.03y )].emit Ha.IJ.Ba np11ema). Ecn11 nauheht He nepehoci1t TaKoi1 pe)f<um nobhiwehi1h.ij.03hi, TO MO)f{HO ysemi411tb HHTepBaJlbl Me)f{)J.y nobbiwehi1simi1 )J.03bl, n1160 nobb!watb.ij.03y 6oJlee nnabho. nph no.ij.6ope.ij.03hi Heo6xo.IJ.I1MO pykobo.ij.ctbobatbch KJ111HH4eCKI1M 3<j>cpeKTOM. Ha4anhHaH.IJ.03a np11 MOHOTepanl111 TOn11paMaTOM y B3pOCJlbiX COCTaBn5leT I 00 Mr B CYTKH, a MaKCI1MaJ1bHaH cyt04hasi )J.03a He.IJ.OJl)f{Ha npebbiwatb 500 Mr. HeKoTopbie nauhehthi c pe<j>paktephbimh cpopmami1 3n11nenc11u nepehocsit MOHOTepan1110 TOnHpaMaTOM B )J.03aX )1.0 I 000 Mr B CYTKI1.,[(aHHbie pekomeh)j.au~ih no )J.0311pOBaHI110 OTHOCSITCSI KO BCeM B3pOCJlbiM, BKJ1104aSI nmkhnhix nauhehtob, 6e3 3a6oneBaHHH n04ek. JVfoHomepamm: ijemu,[(ethm B B03pacTe CTapwe 2 net B nepbyio He)J.eniO ne4ehhsi cne.ij.yet )J.aBaTb TOm!paMaT B )J.03e 0,5 - I Mr/Kr MaCChi Tena nepe.ij. CHOM. 3aTeM.IJ.03Y nobbiwaiot c HHTepsanoM B I - 2 He)J.eJll1 Ha 0,5 - I Mr/Kr B cytki1 (cyt04hyio.ij.03y.ij.enht Ha.IJ.Ba npuema). Ecnu pe6ehok He nepehocih TaKoH pe)f{hm nobbiwehi1si )J.03bl, TO MO)f{HO nobbiwatb )J.03Y 6onee nnabho 11n11 yseni1411batb 11HTepBaJ1bl Me)f{)J.y nobbiwehhsimi1 )J.03bl. 8eni1411Ha )J.03bl II CKOpOCHI ee nobbiwehhsi )J.On)f{Hbl onpe)j.enhtbcsi KJ111HI14eCKI1M pe3ynbtatom. " PeKOMeH)J.yeMbiH )J.Hana30H )1.03 np11 MOHOTepamm TOn11paMaTOM y )J.eTeH B B03pacTe CTapwe 2 net COCTaBnHeT Mr/cyTKI1.,[(eTSIM C He)J.aBHO )J.HarHOCTHpOBaHHbiMI1 napuhaj1bhbimi1 nphna)j.kamh MO)f{HO Ha3Ha4aTb ) Mr B CYTKH. Murpeub PeKOMeH.IJ.yeMaH o6uj,ah cyt04hah.ij.03a TonupaMaTa.IJ.nH npocpunakthkh nphctynos MHrpeHI1 COCTaBJlSieT 100 Mr, nphhhmaei\-iasi 8 2 npllema. 8 Ha4ane ne4ehhsi nauheht )J.On)f{eH np11hhmatb no 25 Mr npenapata TonaMaKc nepe.ij. CHOM B Te4eHHe l He.IJ.emi. 3aTeM.IJ.03Y ysem14hbaiot c lihtepsanom B I He.IJ.eniO Ha 25 Mr B cytkh. Ecnu nauheht He nepehocht TaKoro pe)f{hma nobhiwehml )J.03bl, TO MO)f<HO ysenh4htb HHTepBaJlbl Me)f{)J.y yseml4eh~isimh )J.03bl, n1160 nobbiwatb )J.03Y 6onee nnabho. np11 no)j.6ope )J.03bl Heo6XO)J.HMO PYKOBO)J.CTBOBaThCSI KJ1liHH4eCKI1M 3<j><j>eKTOM. Y HeKOTOpbiX nauhehtob nono)f{htejlbhbih pe3yjlbtat )J.OCTHraeTCSI nph cyt04hoh )J.03e TOnHpaMaTa 50 Mr. 8 KJ111HH4eCKHX HCCne)J.OBaHH51X nauhehtbl nony4anh pa3!1114hble CYT04Hhle )J.03bl TOnHpaMaTa, HO He 6onee 200 Mr B CYTKH. Oco6bte zpymtbt llat(ueumon 1. flo'le'iiwr HeiJocmamo'IHOCI11b nauhehtam C ymepehhoh HJlH TSI)f{enoll no4e4hoh He)J.OCTaT04HOCTbiO MO)f{eT noha)j.06htbcsi CHJI)f{eHHe.IJ.03hi. PeKoMeH.IJ.yeTcH npumehehi1e nonobhhhi pekomeh.ij.yemoh Ha4aJ1hHOI1 11 nomep)f{hbaiomei1.ij.03hi. 2. re.hovua7l/3 nockonhky TOmtpaMaT y.ij.ansietcsi 113 njla3mbl nph remo)j.haj1h3e, B )J.HH npobe)j.ehhsi remo)j.ilaj1h3a cne.ij.yet BBO.IJ.HTh )J.ononHHTenhHYIO.IJ.03y npenapata TonaMaKc, pabhyio npt1mepho nojlobjme CYT04HOH )J.03bl.,[(ononHHTenbHall )J.03a )J.OJl)KHa 6biTb pa3)j.eneha Ha )].Be )J.03bl, nphhhmaembie B Ha4ane 11 nocne 3asepweHwi npoue.ij.yphi remo.ij.haj1h3a.,[(ononhhtenbhah.ij.03a MO)f{eT sapbhposatb s 3aBI1CIIMOCTH OT xapakteptlchik o6opy.ij.obahjhi, IICnOnh3yeMoro nph npobe)j.ehhh remo)j.haj1h3a. 3. fle tell0 1 lhar 1tedocmamo'IHOCI11b naullehtam C ne4eh04hoh He)J.OCTaT04HOCTbiO ronhpamat cne)j.yet nphmehsitb C OCTOpmKHOCTbiO. 6

7 llo60'ihoe }J.eUCTBHe He)l(enaTeJlbHble peakuhh nphbejj.ehbl c pacnpejj.enehhem no 4aCTOTaM 11 chctemam oprahob. ljactot)' He)l(eJlaTeJlbHbiX peakuiih KJlaCCH<pHUHpOBaJlH CJleJJ.yiOW.HM o6pa30m: O'-leHb 4aCTO (~J/10), 4aCTO (~ J/100, <1/10), He'-laCTO (~J/1000 H <11100), pejj.ko (~ <1/1000), O'-leHb pe}j.ko (< , BKJ1104aSI OT}J.eJlbHble CJly'-laH) H 4aCTOTa HeH3BeCTHa (4aCTOT)' HeB03M0)1(H0 OUeHHTb no HMeiOlli,HMCSI,ll.aHHbiM). Ha116onee 4aCTbiMH He)l(enaTeJlbHbiMH peakuhsimh (4aCTOTa KOTOpbrX 6brna 6onee 5 % H npebbllllajla TaKOBYIO B rpynne nnaue6o no KpaHHeH Mepe }J.J1SI O,li.HOfO 113 noka3ahhh B XO,ll.e KOHTp011HpyeMbiX KJ1HHH4eCKHX HCCJ1e,li.OBaHI1H TOnHpaMaTa) SIBJlSIIOTCSI: ahopekchsi, nohh)i(ehhe annen1ta, 3aMe}J.J1eHHOe MblllJJleHHe,,ll.enpeCCHSI, HapyllleHHSI CB060JJ.HOH pe4h, 6eCCOHHHUa, HapyllleHHSI KOOp,li.HHaUHH )J.BH)I(eHHll, HapyllleHHe KOHUeHTpaUHH BHHMaHHSI, fojlobokpy)l(ehhe,,li.h3aptphs1,,li.hcfeb3hsi, rhnecte3hsi, 3aTOpMO)I(eHHOCTb, HapyllleHHSI namsith, HHCTarM, napecte3hsi, COHJlHBOCTb, TpeMOp,,li.HnnonHsr, He'-leTKOCTb 3peHHSI,,li.Hapesr, TOlllHOTa, yctanoctb, pa3,ll.pa)i(htej1bhoctb H nohh)i(ehue M8CCbl TeJla. HHrjJeKZillll u IIH8a3uzt: O'-leHb racto: Ha3oQ>apHHnn*. ' Hap_\ wehur co cmopohbl n:poeu 11 JIIL\1(/Jamu'lecn:oii cucme.ltbl: '-I acto: ahei\ihsi; He'-lacTo: neftkonehhsi, JlHMcpaJJ.eHonanUI, TpOM60UHTOneHHSI, 303HHOCpH11HSI; pe,li.ko: HeHTponeHHSI*. HapyzueHuR co cmopanbl ZLlL\I)'NNazi cucme.llbl: 4aCTO: nmep4ybctbhtej1bhoctb; 48CTOTa HeH3secTHa: aj111eprh JeCKHH OTeK*, OTeK KOHbiOHKTIIBbl*. HapyUtemm co cmopahbl.\lema6ajlli3.\/g u nunwhur: 4acTo: ahopekc~ui, nohh)i(ehhe annethta; He racto: MeTa6onH4eCKHH auh.li.03,.. mnokanhemhsi, nobbjlllehhe annenna, nom1jj.hnchsr; pe.uko: nmepx11opemh4eckhh 8UH.U03, rhnepammohiiemhsi, nmepammohhemh4eck8si 3HUecpanonaTHSI. llcw:u'lecklle HapyzueHl/R: O'-leHb racto: )J.enpeCCHSI; 4aCTO: 3aMe}J.J1eHHOe MblllJJleHHe, 6eCCOHHHUa, HapyllleHHSI CB060)J.HOH pe4h, Tpesora, cnytahhoctb C03H8HHSI,,ll.e30pHeHTaUHSI, arpecchbhbje peaki..lhh, HapyllleHHSI HaCTpOeHHSI, B036y)l(.[leHHe, 3MOUHOHaJlbHaSI Jla6HJ1bHOCTb,,ll.enpeCCHBHOe HacTpoeHue, rhea, HapyllleHue nose.uehhsr; He'-laCTo: cyhu11.ll.ajlbhble MbtcnH, nonbttkh cyhuh.ll.a, f aj11110uhhauhh, nchxotij'-ieckhe pacctpohctba, CJlYXOBble faj1j110uhh8uhh, 3pHTeJ1bHbte f ajljliouhhauhh, anantsr, 3aTpy.UHeHHaSI pe4b, HapyllleHHSI CHa, acpcpektiibhasi na6hj1bhoctb, CHH)f(eHHe Jl i16h)j.o, B036y)f(.[leHHOe COCTOSIHIIe, nlla'-1,.uhccpemhsi, 3HcpOpl14eCKOe HaCTpOeHHe, napahohsi, nepceaepauhsi MblllJJ1eHI1SI, nahh'-ieckhe atakh, nnakchboctb, HapyllleHHe HaBbiKOB 4TeHHSI, HapyllleHHe 3aCbtnaHI1SI, ynllolll,ehhe 3MOUHH, natoj10fh4eckoe MblllJJleHHe, notepsr mt6h)j.o, BSIJlOCTb, llhtpacomhh'-ieckoe pacctpohctbo, paccesihhoctb, pahhiie npo6y)f(.[lehhsi no ytpam, nahh'-ieckhe peakuhh, nphno,li.hsitoe HaCTpOeHHe; pe,li.ko: MaHWI, nahh'-ieckoe pacctpohctbo, 4YBCTBO Oe3blCXO.UHOCTH*, fllnomahhsi. Hapyweuzm co cmopallbl Zleumpa7buozi llepehoii cucme.\lbz: O'-leHb 4acTo: napecte3hh, cohjlhboctb, fojlobokpy)kehhe; 4aCTO: HapyllleHHe KOHUeHTpaUHH BHHMaHHSI, HapyllleHHe namsith, amhe3hsi, KOfHIJTIIBHble pacctpoiictba, ~JapyweHHe l\lblwjlehhsi, nchxomotophbte HapyweH~ISI, CY.UOpOrH, HapyllleHHe KOOp.UHHaUilll )J.BJ1)1(eHI1H, TpeMOp, 3aTOpMmKeHHOCTb, nmecte3hsi, HHCTarM,,DJICfeB311SI, HapyweHHe 4YBCTBa 6anaHCa, )J.H3apTpHSI, 11HTeHU110HHblH TpeMOp, Ce,UaUHSI; He'-laCTO: yrhetehhoe C03HaHHe, TOHHKO-KJ10HH4eCKHe npuna,li.kh no Tltny <<grand rna)», HapyllleHI Ie nojlsi 3peHHSI, CJ10)f(Hbte napl..lllajlbhble nphna)j.kh, HapyllleHHe pe4h, nciixomotophasi nmepaktiibhoctb, 06MOpOK, CeHCOpHble HapyllleHHSI, CJ110HOTe4eHI1e, mnepcomhiisi, acpa311si, nobtopsiiolll,asicsi pe4b, rhnokiihe3hsi, Jl.HCKHHe3HSI, noctypanbhoe fojlobokpy)f(ehhe, HII3KOe Ka'-leCTBO CHa, OLUyLUeHHe )f()f(ehhsi, notepsr 7

8 'IYBCTBUTeJlbHOCTll, napocmhsi, uepe6pajjbhbih CIIH.UpOM,,UH3eCTe3H.R, runoreb3h.r, CTynop, HeyKJJJOJKeCTb, aypa, areb311.r,.nucrpa j>h.r,.nuc j>a311.r, nepu j>eph4ecka.r Hei1ponanm, npe.no6mopo4hoe COCTO.RHHe,.U~ICTOHWI, OIUYIUeHHe "MypaweK" no Teny; pe.uko: anpakcwi, HapyweHHe UHpKa,UJ10f0 phtma CHa, runepecte3h.r, rhnocmii.r, ahocmh.r, 3CCeHU11aJJbHbiH TpeMop, akhhe3h.r, OTCYTCTBUe peakuhh Ha pa3,npajkhtejlllo HapymeHzm co cmopohbl opzaha 3peHzm: YacTo: HeYeTKOCTb 3peHH.R,.UHnnonH.R, HapyweHIIe 3peHH.R; He4aCTO: ymehbwehhe OCTpOTbl 3peH~I.R, CKOTOMa, 1\HIOnH.R*, CTpaHHble OIUyiUeHH.R B rjja3ax*, CyXOCTb rna3, cseto6o.r3hb, 6ne j>apocna3m, nosbjwehhoe cne3ote'jehhe, cpotonc~t.r, MH.UpHa3, npec6uom1.r; pe.uko: O.UHOCTOpOHllii.R CJlenoTa, npexo.u.rlua.r CJlenoTa, rnaykoma, HapyweHHe akkomo.uauhh, HapyweHUe 3pHTeJ1bHOfO npoctpahctbehhoro BOCnpH.RHI.R, MepuaTeJlbHa.R CKOTOMa, OTeK BeK*, H04Ha.R cnenota, am6nuonh.r; YacToTa HeH3BeCTHa: 3aKpb1ToyroJ1bHa.R rnaykoma*, MaKynonanJ.R*, HapyweHH.R no.ubhjkhochi fjla3a* o HapyweHUR co cmopohbl opzaha corzyxa u pa8hoeeczm: YacTo: septhro, 3BOH B ywax, 6onb B yxe; He4aCTO: fjlyxota, O.UHOCTOpOHH.R.R rllyxota, HefipoceHCOpHa.R rnyxota,.uhckom j>opt B yxe, HapyweHHe cnyxao ' Hapywemm co cmopohbl cepije mo-cocyijucmoii cucmeollbz: HeYacTo: 6pa.nuKap.nu.R, CHHycHa.R 6pa.nuKap.nmJ, owywehhe cep.nue6uehj1.ro Hapyzueuzm co cnwpohbl cocyijucmoii cucmeollbz: HeYacTo: nmoteh3h.r, optoctanjyecka.r runoteh3h.r, nphjli1bbl, rop.r4he npiijjhbbl; pe.nko: j>ehomeh Pei1Hoo Hapyzuemm co cnwpohbl dbzxmneo'lb1taii cucmeollbl, opzahob zpyijuoii K.rzemKu u cpedocmemm: 'JaCTo: O.UbiWKa, HOCOBOe KpOBOTe4eHHe, 3WlOJKeHHOCTb HOCa, phhope.r, KaWeJlb*; He4aCTO: O.UbiWKa nph j>h3h4eckoh Harpy3Ke, runepcekpeuj I.R B nph,uat04hbix na3yxax HOCa,.UHC j>oh~o HapyzueHZm co cmopohbl.jiceorzydol{ho-kliutel{hozo mpakma: 04eHb YacTo: TOWHOTa,.nuape.R; YacTo: psota, 3anop, 6onb B ::muractpanbhoi1 o6nacth,.nucnencu.r, 6onb s ilnjbote, cyxoctb so pry,.uiickom j>opt B /Keny,nKe, HapyweHHe 4YBCTBHTeJ1bHOCTH B potoboh nojlocth, ractpht,.uhckom j>opt B /KHBOTe; HeYacTo: nahkpeann, MeTeopH3M, ractp033o j>areanbhbli1 pe j>njokc, 6onb B HH)f(HeH LJacnl JKIIBOTa, CHHJKeHHe 4YBCTBI1TeJ1bHOCTH B potoboh nojlocth, KpOBOT04HBOCTb.neceH, B3.UYTHe JKHBOTa,.UIICKOM j>opt B 3nHracTpMbHOH 06JlaCTH, 4YBCTBHTeJlbHOCTb B 06JlaCTH IKHBOTa, nmepcanhbauh.r, 6 0Jlb B potoboh nojloctii, HenpmlTHbiH 3anax H30 pta, rjlocco.uhhh.ro Hapyweuzm co cmopohbl <' enamo6uorzuaphozi cucmeohbz: pe.nko: renantt, He,UOCTaT04HOCTbo HapyzueHuR co cmopohbl ~-.:o;)fcu 11 noijhoo;)fchblx oauezi: YacTo: anoneuh.r, Cblnb, 3y.n; HeYacTo: ahnt.up03, HapyweHHe 4YBCTB~ITeJlbHOCTII B 06JlaCTl1 JlHUa, KpamtBHHUa, 3p11TeMa, rehepami30bahhbih 3Y.U, MaKyll.RpHa.R Cblnb, HapyweHIIe mtrmehtauhl1 KOJKH, ajjjlepru4eckhh.nepmatht, nphnyxjjoctb n uua; HeYacTo: CHH.npoM CnmeHca-,lJ;JKOHCOHa*, nomtmop j>ha.r 3pHTeMa*, H3MeHeHHe 3anaxa KOJKH, n apaop611tajjbhbih OTeK*, J10KaJJH30BaHHa.R KpanHBH11Ua; 4aCTOTa HeH3BeCTHa: TOKCH4eCKHH :mu.nepmanbhbih HeKpom13* 0 Hapyzu e/-ll/fl co cmopohbl Choe!lemuo-.llb/llle'IIIOli cucme.llbl ll coeol/1-ll/111e.rzbholi 111KQH11: LJaCTO: a ptpannt.r, MbJWe4HbJe cna3mbl, MHMrii.R, MbiWe'J~Ible cy.nopont, MbJWe'JHa.R cna6octb, ckenetho M bjw e YHa.R 60Jlb B rpy.uhoh KJleTKe; He4aCTO: npunyxjjoctb cyctabob*, CKOBaHHOCTb MbiWU, B 6oKy, YCTMOCTb B MbiWUaX; pe,uko:.u11ckom j>opt B KOHe4HOCT.RX*o 8

9 HapyzueHIIR co cmopohbl notteh u.1/ottebbu:worll/lix nymeii: LJacTo: HecpponHTIIa3, nonnakhyp11.sl, tj,h3yp1ul; HettaCTO: o6octpe~tlle MOLJeKaMeHHOH 6one3HH (KaMHH B noljkax), He.[l.ep:a<aHHe MO'-IH nph HanpsnKemm, rematyphst, He.a.ep'iKaHHe MOLJH, LJaCTble no3b1bbt K MOLJeucnycKaHmo, noljeljhast KOJlHKa, 6onH s o6nacth noljek; pe.a.ko: o6octpehue MOLJeKaMeHHOH 6one3HH (KaMHH s ypetpe), nolje'-ihok8hajlbl..(ebbih 81..(H.[I.03*. HapyztteHzm co cmopohbl no.riobblx opzahob u.1/0jiotthoti J/CeJle3bl: HeLJaCTo: 3peKHUibHast AHCcpyHKUHst, cekcyajlbh8ll.[i.hccpyhkuhll. 06utue paccmpozlcmba u HapytaeHZm, o6yc.'iob.'lehhble cnoco6o.11 np!l1reue111m: oljehb LJacTo: yctajloctb; '-18CTO: nobbiwehh8ll TeMnepaTypa Tena, 8CTeHHll, p83.[1.pmkhtejlbhoctb, HapyWeHHll noxo.a.kh, nnoxoe camoljysctbhe, 6ecnoKoi1cTso; HeLJacTo: nmeptepmhst, )Ka'iKtJ,a, rp1mnono.a.o6hbih chhapom*, Me.[I.JlHTenbHOCTb, noxono.a.ahhe KOHeLJHOCTeH, LJYBCTBO onbsthehmi, ow.ymehhe 6ecnOKOHCTBa; pe.[j.ko: OTeK JlHI..(a, KaJlbi..(HH03. Jh.lteHeHue.'la6opamopHblX nokmame.'lezi: oljehb LJacTo: CHH'iKeHHe MaCCbl Tena; LJacTo: ysemtljehhe M8CCbl Tena*; HeLJaCTO: KpHCTaJlJlypHst, 8HOMaJlbHbiH pe3yjlbt8t TeCTa «T8H.[I.eM-nOXO.[I.K8», nehkonehhll, nobbiwehi1e 8KTIIBHOCTH neljeho'-ihbix cpepmehtob B CbiBOpOTKe KpOBH, pe.[j.ko: ymehbwehi1e CO.D.ep'iK8HHll rh.[j.pokap60h8tob B KpOBH. Hapywemm colfuojlbh020 rfjyhh"lfll01111pobalwr: HeLJacTo: HapyweHHe cnoco6hocth K o6yljehiho. * - He'iKeJlaTeJlbH8ll peakuhll 3apentCTpHpOBaHa B noctpen!ctpauhohhom nepho.[i.e H3 CnOHT8HHbiX coo6w.ehhh. 4aCTOTa pacc'-ihtaha Ha OCHOB8HHI1.[1.8HHbiX KJlHHHLJeCKHX IICCJle.[I.OB8HHH. Oco6ble rpynnbl: llem: HH'iKe nphbe.[l.eh CnHCOK He)KenaTeJlbHbiX peakuhh, KOTOpble B XOtJ,e KOHTp01111pyeMbiX KJ111HHLJeCKHX IICCJletJ,OB8HHH peructphpobajlhcb y.[l.eteh B 2 II 6onee pa3 '-law,e, t(em y B3pOCJlbiX: nomt'ikehhe annen1ta, nobbiwehhe annethta, mnepxnopel\hiljeckhh auha03, nmokanhemhst, HapyweHH.ll nose.a.ehhll, arpecchbhble peakuh11, anatiill. HapyweHHe 38Cbtn8HHll, cyhuh.[i.ajlbhble MbiCJlH, HapyweHHe KOHUeHTp8UIIIl BHIIM8HH.ll, 38TOpMO'iKeHHOCTb, HapyweHHe UHpKa.[I.HOrO phtma CHa, HH3KOe KaLJeCTBO CHa, nobbiwehhoe CJle30TeLJeHHe, CUHYCH8ll 6pa.[I.I-IK8p.[J.Hll, nnoxoe CaMO'-IYBCTBHe, HapyWeHHll noxo.[i.kh. HH'iKe nphbe.[l.eh CmiCOK He)J<eJlaTeJlbHbiX peaki..(iih, KOTOpble B XO.[I.e KOHTpOnHpyeMbiX KJlHHHLJeCKHX UCCJle.[I.OBaHHH perhctphpobajlhcb TOJlbKO y.[l.eteh: 303H1-10cpHJ1Hll, nchxomotophast runepakthbhoctb, sepmro, psota, nmeptepmhst, mtpekchst, HapyweHHe cnoco6hocth K o6yljehmo. 0epet~,03UpOBK3 nph3h8ki1 H Clil\1nTOMbl nepe.d.03hpobkh npenapata TonaMaKc : cy.a.opom, COHJlHBOCTb, HapyweHIIll pe'-111 H 3peHilll,.[l.ltnJlOmlll, HapyweHHll MbiWJleHHll, HapyweHilll K00p.[I.HH81..(1111.[I.BH'iKeHHH, JleTaprHll, crynop, aptephanbhast nmoteh311st, 6onb s 'iki1bote, ronosokpy)kemte, B036y'iKtJ,eHHe H.a.enpeccHst. B 6onbWHHCTBe cnyljaes KJlHHHLJeCKite nocnetj,ctbhst He 6biJlH Tst'iKenbiJ\Ht, HO 6biJlH OTMeLJeHbl CMepTeJlbHble cnyti3h nocne nepe.[j.03hpobki1 C IICnOJlb30BaHIIeM CMeCI1 HeCKOJlbKHX JleKapCTBeHHbiX cpe.[j.ctb, BKJl~LJast TOmtpaMaT. nepe.[i.0311pobka TOmtpaMaTa MO'iKeT Bbi3BaTb Tll'iKeJlbiH MeTa6omttleCKHH auu.a.o3 ( CM. pa3.a.en «0co6ble yka3ahhst» ). ltbsecteh cnytmfi nepe.a.o3hpobkh, Kor.a.a nauheht np11hstn A03Y TomtpaMaTa OT 96.a.o 110 r, '-ITO nosnekjlo 38 co6oi1 KOMy, npo.[j.ojl'ik8bwy~cll BepHyJlOCb B HOpMy LJaca. CnyCTll 3-4.[I.Hll COCTOliHHe nauhehta 9

10 Jle'leflue. npu octpoi1 nepejj.03uposke npenapata Tonai\JaKc, ec11u He3a)J.o11ro nepea 3THM 6o11bHOH npuhhman numy, He06XO)J.I1MO Cpa3y )Ke npombitb )Ke11y)J.OK H11U Bbi3BaTb pboty. 8 11CC11e)J.OBaHWIX in vitro 6bl110 noka3aho, 4TO akthbhpobahhbih yr011b a)j.cop6upyet TOnllpaMaT. np11 Heo6XO)J.I1MOCT11 CJle)J.yeT npobecth CHMnTOMaTII'IeCKYIO TepanHIO. 3cpcpeKTHBHbiM cnoco60m BbiBe)J.eHHH TOnHpaMaTa 113 oprahi13ma HB11HeTCH remo)j.haj1u3. naujiehtam pekomeh)j.yetch a)j.ekbathoe nobblwehiie 06beMa notpe611hemoh )1(11)J.KOCTI1. BJaltMO)J.eiicTBIIe c JJ.pyrnMII nekapctbehhbimii npenapatamn Bmmuue upemtpama TolllUUIKC 11(1 KO/It(ellmptll(llll opyzux 11p :Jillutelllllll'leCKliX upemtpamob (ll3ll) 0)J.HOBpeMeHHbiH nphem npenapata TonaMaKc c APYfHMH n3n (cj>ehhtohh, Kap6aMa3eni1H, BaJ1bnpoeBaH KUC110Ta, cpeho6ap6htaj1, nphmh)j.oh) He OKa3biBaeT B1111HHHH Ha 3Ha4eHHH IIX pabhobechbix KOHUeHTpaUHH B n11a3me, 3a UCKJ1104eHHeM OT)J.e11bHbiX 6011bHbiX, y KOTOpblX A06as11eHue npenapata TonaMaKc K cj>ehhtohhy MO)I(eT Bbi3BaTb nobbiwehue KOHUeHTpaUHH cpehhtoiiha B n11a3me. JTO MO)I(eT 6b1Tb CBH3aHO C yrhetehuem cneuucp114eckoh 1130cpOpMbl cj>epmehta C~ICTeMbl nomimopcphoh UHTOXpOMa P450 (1130cpepMeHTa CYP2C 19). no3tomy y Ka)I()J.oro 6011bHOfO, KOTOpblH nphhiimaet cpehhtohh 11 y KOTOpOrO pa3bhbaiotch KJ1HHH4eCKHe nph3hakh CIIMnTOMbl TOKCI14HOCTI1, He06XO)J.HMO C11e)J.HTb 3a KOHUeHTpaUIIeH cpehhtoi1ha B n11a3me. 8 11CC11e)J.OBaHIII1 cpapmakokiiheti1kh y 6011bHbiX 3n1111enc11ei1 )J.06aB11eHI1e TOmtpaMaTa K 11aMOTp11)J.)I(I1HY He B1111H110 Ha pabhobechyio KOHUeHTpaUHIO noc11e)j.hero nph )J.03aX TOnHpaMaTa ) Mf B CYTKH. 8 npouecce Tepamm 11 noc11e OTMeHbl 11aMoTpHJJ.)KHHa (cpeahhh A03a 327 Mr B cytkh) pashosechah KOHUeHTpaUIIH TOn11paMaTa He H3MeHSIJ1aCb. BOJ()eilcmBUe opyztix 11p :Jillutellmll'leCKliX upetwpamoa /ttl KOilt(eumpat(IIW upemtpttnltl Tomuw«c <llehhtohh 11 Kap6aMa3emtH CHI t)l(a!ot KOHUeHTpaumt npenapata TonaMaKc s n11a3me.[(o6as11eh11e OTMeHa cj>ehi1tohha I tm1 Kap6aMa3emtHa Ha <jlohe 11e4eHIIH npenapatom TonaMaKc MO)I(eT notpe6osatb InMeHeHHH A03bl noc11e)j.hero..[(o3y c11ejj.yet no)j.611patb, opuehn1pyhcb Ha )J.OCTIDKeHHe He06XO)J.I11\IOfO KJ111Hll4eCKOfO 3CpcpeKTa..[(o6aB11eHIIe OTMeHa BaJlbnpoeBOH KI1C110Tbl He Bbl3biBaeT KJ111HH4eCKI1 3Ha4HMbiX H3MeHemti1 KOHUeHTpau~IH npenapata TonaMaKc s nna3me 11, C11e)J.oBaTe11bHO, He Tpe6yeT mmehehhh A03bl npenapata TonaMaKc. Pe3y11bTaTbl :nux B3aHMOAei1cTBI1i1 cymmhposahbl s c11ejj.y10mei1 Ta611uue: J(o6aa.Ttne.m,,l ll3ll Kom(eumpm(ttR ll3ll Kom(eumptll(IIR upeuapama TotUUillKC C/JeHumouH H** j, (48%) Kap6a.\tC/3el1ltfl f-7 j, (40%) Ba.1 bnpoebc/jl K uc.rwnw f-7 f-7 C/Je11o6ap6umcLT1 f-7 HH 17 pu. HuiJoH f-7 HH ~ = 0TcyTCTBHe 3cpcpeKTa ** = nobbiwehhe KOHUeHTpaUIHI y e)j.iihh'ihbix 6011bHbiX! = Cmt)l(emte KOHueiHpau~m s n11a3me HH = He ucc11e)j.osanacb H3n = nponiso:mh11enth4eckui1 npenapat 10

11 ,L(pyrne JieKapCTBeiiHble BJaiiMO~eHCTBHH puc:okcuh: B uccne~osahhi1 c ucnonbjobahi1em o,nhokpathoh.lj.03bi nnoma,nb no.n KpHBOH AUC ( «KOHU,eHTpau,ml-speM51»),n11roKc11Ha B nna3me np11 o,nhospemehhom npueme npenapata TonaMaKc ymehbwajlacb Ha 12 %. KmtHH4eCKa51 3Ha4HMOCTb :noro Ha6mo,neHI151 He 51CHa. np11 Ha3Ha4eHI1H OTMeHe npenapata TonaMaKC 60JlbHbiM, np11hhmaioluhm,!j.hfokchh, OC06oe BHHMaHHe He06XO,!J.I1MO y,nejjhtb MOHHTOp11pOBaHHIO KOHU,eHTpaU,HH,!J.I1fOKCHHa B CbiBOpOTKe. Cpeocmea, yc:hemmout-ue I.{HC: B pamkax KJli1HH4eCKHX 11ccne.nosaH11H nocne,nctbi151 o,nhospemehhoro np11ema npenapata TonaMaKc c ankoronem 11m1.npyri1MH semectbamh, yrhetatoluhmh cpyhku,hi1 UHC, He H3Y4aJ111Cb. PeKoMeH,nyeTc51 He np11hi tmatb TonaMaKc BMecTe c ankoronem HJ111.npyrHM~t npenapatami1, Bbt3biBatOlUHMI1 yrhetehi1e cpyhku,i111 UHC. 3eepo6oii npooblprb.llehhbtit np11 COBMeCTHOM npheme TonaMaKca 11 npenapatob Ha OCHOBe 3Bepo6051 npo,lj.b1p51bjlehhof0 (Hypericum pe!foratum) KOHU,eHTpaU,H51 TOn11paMaTa B njja3me MO)KeT CHI1)KaTbC51 11, KaK CJle,LJ.CTBHe, 3cpcpeKTHBHOCTb npenapata TaK*e MO)KeT nohh311tbc51. Km!HH4eCKI1X IICCJJe,nosaH~IH B3aHMo.nel1cTBH51 npenapata TonaMaKC H npenapatob Ha OCHOBe 3Bepo6051 npo,lj.blp51bjlehhoro He npobo,!j.i1jl0cb.!jepopculbllb/e k"011111pat{el1111ll8b/: B HCCJle,LJ.OBaHHH JleKapCTBeHHOfO B3aHMO,LJ.eHCTBH51 C nepopanbhbimh KOHTpau,enTHBaMH, B KOTOpOM HCnOJlb30BaJ1C51 KOM6HHHpOBaHHbiH npenapat, co,nep)kaluhh HOp3TI1CTepOH (1 Mf) 11 3THHI1Jl3CTpa,nHOJl (35 MKf), TonaMaKC B,!J.03aX Mf B,LJ.eHb He OKa3biBaJ1 cyluectbehhofo BJlH.SIHH51 Ha 3cpcpeKTHBHOCTb HOp3THCTepoHa H B,!J.03aX Mf B,LJ.eHb - Ha 3cpcpeKTHBHOCTb 3THHHJl3CTpa.nuo-na. CymecTBeHHoe,no3o3aBHCI1Moe CHH)KeHHe 3cpcpeKTHBHOCTI1 3Tt1HwncTpa~uona Ha6ntO,nanocb np~t,n03ax npenapata TonaMaKc Mr B,neHb. KmtHH4ecKa51 3Ha4HMOCTb Om!CaHHbiX H3MeHeHHH He 51CHa. PHCK CHH)KeHH.SI 3cpcpeKTHBHOCTH KOHTpau,enTHBOB H ycunehlf51 «npopbtbhbtx» KposoTe4eHHi1.LJ.OJl)KeH Y4HTbtBaTbC51 y 6onbHbtX, nphhhmatoluhx nepopanbhbie KOHTpau,enTHBbt B co4etahhh c npenapatom TonaMaKc. oojlbhbtm, nphhhmatoluhm ::>CTporeHco.nep)!<amue KOHTpau,enTHBbt, Heo6xo,nHMO coo6matb o Jlt06btX 113MeHeHH51X B cpokax 11 XapaKTepe MeHCTpyau,HiJ. 3cpcpeKTIIBHOCTb KOHTpau,enTHBOB MO)KeT 6btTb CHH)KeHa,na)Ke nph OTCYTCTBHH «npopblbhbix» KpOBOTe4eHHH. Jlumuzi: y 3,nopoBbiX.no6posonbu,es Ha6ntO,nanocb CHH)KeHHe AUC JJHTH51 Ha 18% npu 0.[\HOBpeMeHHOM np11eme TOnt1paMaTa B.[\03e 200 Mf B CYTKH. Y 60JlbHbiX C MaHHaKaJlbHO,nenpeCCHBHbiM nchx030m nphmehehhe TOnHpaMaTa B,LJ.03aX.[\0 200 Mf B CYTKH He BJllHIJlO Ha cpapmakokhhethky Jli1TH51, o,nhako npu 6onee BbtCOKHX,n03ax (.no 600 Mr B cytkh) AUC JJHTH51 6btJla nobbiweha Ha 26%. npu 0.[\HOBpeMeHHOM nphmehehhh TOnHpaMaTa 11 Jli1TH51 CJle,nyeT KOHTp011HpOBaTb KOHU,eHTpaU,HIO nocjle,nhero B njla3me KpOBH. Pucnepuoou: uccne.nosahh.si nekapctsehhoro B3aHMo,nei1cTBH51, npose,nehhbte c o.nhokpathbtm 11 MHOfOKpaTHbiM nphemom TOnHpaMaTa 3.[\0pOBbiMII,no6pOBOJlbU,aMH 11 60JlbHbiMH C 6HnO!l51pHbiM pacctpohctbom,.[\ajlh O.D.I1HaKOBbte pe3yjlbtatbl. np11 O,!J.HOBpeMeHHOM np11eme TOnHpaMaTa B,!J.03aX 250 t!jll1 400 Mr B cytktt AUC pucnepu,noha, np11hhmaemoro B,n03ax 1-6 Mr B cytkh, chmkaetc51 COOTBeTCTBeHHO Ha 16% 11 33%. npu 3TOM (papmakokhhetitka 9-rH,npOKC11pHCnepH.D.OHa He 113MeH51JlaCb, a cymmapha51 cpapmakokhhethka akthbhbix Bell.leCTB (phcneph.l\oha 11 9-ru,npOKCIIpHCnepH,LJ.OHa) H3MeH51JlaCb He3Ha4HTeJlbHO. I13MeHeHI1e C~ICTeMHOfO B03,neikTBH51 pllcneph,!j.oha/9-ru,npokchp11cneph.d.oha 11 TOm!paMaTa He 6biJ10 KJlHHH4eCKI1 3Ha4HMO, H 3TO B3aHMO.LJ.eHCTBHe Bp51,n JlH MO)KeT HMeTb KJli1HH4eCKOe 3Ha4eHHe. II

12 FuiJpox.'lOpOnll/03110: JleKapCTBeHHOe B3aiiMO.UeHCTBHe OU.eHHBaJlOCb Ha 3.UOpOBbiX.UOOpOBOJlbU.aX npu pa 3,neJ1bHOM II COBMeCTHOM nphmehehhu rh.upox!10p0tiia3h.ua (25 Mr) II TOn11paMaTa (96 Mr). Pe 3 ynbtatbt uccne.nosahhh noka3anh, ttto nph o.nhospemehhom npueme TOmlpaMaTa 11 rh,upox!10potiia3h.ua npohcxo,uht ysemllfehue MaKCHMaJlbHOH KOHU.eHTpaU.HH TOmtpaMaTa Ha 27% H nnoma.nh no.n KpHsoi1 AUC TOmlpaMaTa Ha 29%. KmiHHlfecKa51 3HalfHMOCTb 3THX uccne.nosahhh He Bbi5IBJ1eHa. HmHalfeHHe m.npoxnopotha3h.ua nau.hehtam, nphhhmaio!uhm TOmlpaMaT, MO)f(eT notpe6osatb KoppeKU.HH.U03bt TomtpaMaTa. <l>apmakokhhenllfeckue napametpbt m.npoxnopotumu.na He no.nsepranhcb 3Halfi1MOMY H3MeHeHHIO nph conytctbyio!ueh TepanHH TOnHpaMaTOM. MemrjJop.HuH: nekapctbehhoe B3aHMo.nei1cTBHe ou.ehhbmocb Ha 3,noposbtX.no6posonbu.ax, nonyyaswux Menj>Opl\utH unu KOMOHHaU.HIO MeTcpopMuHa H TOmlpaMaTa. Pe3ynbTaTbt Hccne.nosaHHH noka3aj1h, '-ITO nph O.UHOBpeMeHHOM npheme TOnHpaMaTa II MeTQJOpMIIHa npohcxo.u~it ysemllfehue MaKCHMa!lbHOH KOHU.eHTpaU.HH 11 nj10!ua.u11 no.n KpHBOH A UC Menj>OpMHHa Ha 18% H Ha 25% COOTBeTCTBeHHO, TOr,na KaK IU1HpeHC MeTQJOpMHHa nph O.UHOBpeMeHHOM nphmehehhh C TOmtpaMaTOM CHH)f(aJ1C51 Ha 20%. TomlpaMaT HHKaK He 8!11151!1 Ha BpeM51.UOCTH)f(eHH51 MaKCHMaJlbHOH KOHU.eHTpaU.HH Menj>opMHHa B nna3me Kposu. KnupeHc TonupaMaTa npu o.nhospemehhom npumehehhh c Menj>opMHHOM CHH)f(aeTC51. CTeneHb Bbi51BJ1eHHbiX H3MeHeHHH K!lHpeHca He 113YlfeHa. KJlHHHtteCKa51 3HalfHMOCTb B03,UeHCTBH51 MeTcpOpMHHa Ha cpapmakokhhetiiky TOnHpaMaTa He 51CHa. 8 cnyyae.no6asnehh51 HJlH OTMeHbt npenapata TonaMaKc y nau.uehtob, nonylfaio!u~tx Menj>opMHH, cne.nyet T!UaTeJlbHO KOHTp0!111pOBaTb COCT051HHe OOJlbHOrO.UJ151 OU.eHKH TetteHH51 caxaphoro.uhaoeta. flllozlll/111q30h: JleKapCTBeHHOe B3aHMO,UeHCTBI Ie OU.eHHBaJlOCb Ha 3.UOpOBbiX.UOOpOBOJlbU.aX nph pa3.nenbhom H o.nhospemehhom njmmehehhh nuormita3oha H TOnHpaMaTa. obtno Bbi51BJleHo ymehbwehhe nnoma.n11 no.n KpHBoi1 AUC nhornhta30ha Ha 15%, 6e3 mmehehh51 MaKCHMaJlbHOH KOHU.eHTpau.~m npenapata. 3TH H3MeHeHH51 He 6btm1 CTaTIICTHlfeCKH 3HalfHMbtMH.,lV151 aktiibhoro rh.npokciimeta6onnta nhor!lhta3oha TaK)f(e 6btno Bbi51BJ1eHo CHH)f(eHHe MaKCHMa!lbHOH KOHU.eHTpau.HH 11 nnoma.nh no.n Kpusoi1 AUC Ha 13% 11 Ha 16% cootbetctbehho, a AJ151 akthbhoro KeToMeTa6omtTa 6btno Bbt51sneHo CHJI)f(eHHe 11 MaKCIIMaJlbHOH KOHU.eHTpau.ml 11 nnoma.n11 no.n Kpusoi1 AUC Ha 60%. KnHHHlfeCKa51 3HalfHMOCTb 3TI1X.naHHbiX He Bbi51CHeHa. npu O.UHOBpeMeHHOM nphmehehml nau.uehtamh npenapata TonaMaKc 11 mtormita3oha, cne.nyet TlllaTe!lbHO KOHTpom1posaTb coct051h~ie 6onbHoro.nnSJ ou.ehkh TelfeHH51 caxaphoro wm6eta. F:llt6ewv?cL\fliO: 6btno npose.neho uccne.nosahue nekapctbehhoro B3aiiMo.nei1cTBH51 AJ151 lnylfehii51 cpapmakokhhethkh rmioehkjlamh.ua (5 Mr B CYTKH) B pabhobeci10m COCT051HHH, nphmeh51emoro lnomtposahho unu o.nhospemehho c TOmtpaMaTOM (150 Mr B cytkh) y 6onbHbtX caxaphbtm.n11a6etom 2 THna. npu nphmehehuh TOnHpaMaTa AUC rml6ehkj1amu.na CHU)KaJlaCb Ha 25%. TaK)f(e ObiJla CHII)f(eHa CHCTeMHa51 3KCn0311LJ TpaHC-rH.UpOKCH-rmtOeHKJlaMH.Ua H 3-U.HC-r11.UpOKCHrnu6eHKJ1al\HJ,Ua (COOTBeTCTBeHHO Ha 13% II 15% ). fmt6et1kj1al\hj.u He BJ1H51J1 Ha cpapmakokjihetitky TonupaMaTa s pashosechom coct051hhh. 06Hapy)f(eHo ctathctiilfeckh He.nocTosepHoe CHH)f(eHHe AUC nuormtta30ha Ha 15% nph OTCYTCTBHH 113MeHeHH51 Cmax. np11 Ha3HalfeHJIH TOnupaMaTa OOJlbHblM, nonylfaiolu.11m rm16ehkj1amu.u (11m1 Ha3HalfeHHH rnu6ehk!lamh.na 6onbHbtM, nonylfaio!uhm TonHpaMaT), cne.nyet TLU,aTeJlbHO KOHTp0!1HpOBaTb COCT051HHe OOJlbHOrO,UJ151 OU.eHKI1 TelfeHH51 caxaphoro.uhaoeta. J(pyzue npenapambt: O.UHOBpeMeHHOe nphmehehue npenapata TonaMaKc c npenapatamh, npe.npacnonaraiolu,hmh K HecpponHTHa3y, MO)f(eT nobbtwatb phck o6pa3obahh51 KaMHei1 s nolfkax. Bo BpeM51 nettehji51 npenapatom TonaMaKc cne.nyet 1136eraTb np~1mehehi151 npenapatob, 12

13 npe)lpacnonaral0ll.u1x K HecppomtTI1a3y, nockojlbky OHI1 MOryT Bbi3BaTb cpt13110jlofl14eckhe 113MeHeHtHI, cnoco6ctbyiouj,l1e HecppOJJI1TI1a3y. 8aJibnpoeBafl ~-. uc.rwma: KOM6HH11pOBaHHOe np11mehehtte TOnHpaMaTa 11 BaJJbnpoeBOH KI1CJ10Tbl y 6oJJbHbtX, xopowo nepehoc.s~mux Ka)f()l.biH npenapat B OT)leJJbHOCTI1, conposo)f()l,aetc.sj nmepammohhemuei1 c 3HU.ecpanonantei1 11n11 6e3 Hee. B 6oJJblllHHCTBe cnyt.taes CHMnTOMbt 11 np113haki1 11ct.te3aiOT nocne OTMeHbt O.!lHOro m npenapatob (em. pa3jlejj «0co6bte YK33aH11.!1» 11 «no6ot.thoe )lehctb11e»). 3Ta He6naronpH.s!TH3.!1 peaku.h.!i He Bbi3B3Ha cpapm3kokhheth4eck11m B3aHMO)leHCTB~IeM. np11 COBMeCTHOM npheme TOn11paMaTa 11 BaJJbnpoeBOH KHCJlOTbl MO)f(eT B03HHK3Tb ntnotepm11.!1 (Henpe)lHaMepeHHOe CHI1)f(eHHe TeMneparypbl TeJJa HtnKe 35 C) B C04eTaHHI1 C nmepammohhemi1eh HJll1 )f(e He33BI1CI1MO..[(aHHOe.!IBJJeHHe MO)f(eT B03HHK3Tb KaK nocjje Hat.tana COBMeCTHOfO nphema BaJJbnpoeBOH KHCJJOTbl 11 TOnHpaMaTa, TaK 11 np11 ybejjht.tehhi1 )lhebhoh )l03bl TOmtpaMaTa. J{onoJlHUmellbHble ucc.rreooeautm Jle~.:apcmeeuuoc:o B3azwooericmezm: JlJl.!l ou.ehki1 notehu.11ajjbho B03MO)f(HbiX Bap11aHTOB JJeKapCTBeHHOfO B3aHMO)leHCTBH.!I Me)f()l.y TOn11p3M3TOM 11 Jlpyr11MH JJeKapCTBeHHbiMH npenapatam11 6btJl npobe)leh p.s!jl KJJHHI14eCKI1X 11CCJJe)lOB3HHH Pe3yJJbTaTbt 3THX B3aHMO.!leikTBHH cymmhposahbt B cne)lyiouj,eh m6n11u.e:..,l],o6aonhemoe Kou... eutpa... uh,llo6aonhemoro Kou... eutpa... nh nekapctoenuoe cpe,llctbo nekapctoeuuoro cpe,llctoaa TODHpaMaTaa ysejjh4ehi1e MaKCI1MaJJbHOH AMHTpHnTI1JJHH KOHU.eHTpau.~m 11 AUC MeTa6oJJI1Ta He HCCJle)lOBaJJOCb 0 HOpTp11nTI1JJI1Ha Ha 20%.[(u nt.!lp03protam 11 H ( nepopajjbho 11 no)lko)f(ho) fanoneph)lojl H ysejjht.tehi1e AUC MeTa6oJJI1Ta Ha 31% H He 11CCJle)lOBaJJOCb ysemtt.tehi1e MaKCIIMaJJbHOH ysejji14ehhe M3KCHMaJJbHOH KOHU.eHTpaU.HH Ha 9% 11 nponpahojlojl KOHU.eHTp3U.HI1 )ljl.!l 4-QH 16%, ysen11t.teh11e A UC nponpahonona Ha 17% (TonupaMaT Ha 9% u 17%, 50 Mr) COOTBeTCTBeHHO (JlJl.s! nponpahonona 40 Mr Mr Ka)f()l.bte 12 t.tacos) CyMaTplmTaH (nepopanbho 11 no)lko)f(ho) H He HCCJJe)lOBaJJOCb nll30thcpeh H H ymehbwehi1e AUC Jli1JJTI1a3eMa Ha.[(unn1a3eM 25% 11 ymehblllehi1e )le3au.entjjjli1jjtita3ema Ha 18%, 11 ysemtt.tehue AUC Ha 20% H JlJl.!l N-JleMeTHJJJlttJJnta3eMa BeHnacpaKcttH H H <l>jtyhaph311h ysemtt.tehi1e AUC Ha 16% (50 Mr Ka)f()l.bte 12t.t)h H 13

14 a BbipaJKeHa B % OT 3HULieH~IH MaKCHMaJlbHOH KOHUeHTpaUHH B njia3me KpOBH 11 AUC npu MOHOTepani1H +-+ = 0TcyTCTB11e 113MeHeHHH MaKCHMaJibHOH KOHUeHTpauuu B njia3me KpOBH 11 AUC (~ 15% ot HCXO.[J.HbiX.[J.UHHblX) b npu MHOfOKpaTHOM npueme O)J,HOfO cj)j(yhapmhha Ha6JIIO)J,aJIOCb ysejihliehhe AUC Ha 14%, LITO MOJKeT 6biTb CBSI3aHO C HaKOnJieHHeM npenapata B npouecce )J,OCTHJKeHWI pabhobechofo COCTOSIHII.SI. Oco6Lie ykajanuh npothbo:mhjienthlieckhe npenapatbl, BKJIIOLia.SI 11 npenapat TonaMaKc, cne.nyet OTMeHSITb noctenehho, LIT06bi csecn1 K MHHHMYMY B03MOJKHOCTb nobbiwehh.si LiacTOTbi nphna.nkob.,llnsi ymehbwehh.si.d.olbi Ha Mr HCnOJib'3.)'10T npenapat TonaMaKc Kancyllbi B.D.OlllpOBKe 15 Mr HJIH 25 Mr. 8 KJIIIHHLieCKHX IICCJie,D.OBaHH.SIX )J,0'3bl.)'MeHbWaJIH Ha 50-J 00 Mf C He,D.eJibHbiMH HHTepBaJiaMH.[J.JISI B3pOCJibiX nph TepamiH :mhjienchh H Ha Mf.)' B3pOCJibiX, noji.)'liaiou(i1x 100 Mr npenapata TonaMaKc B cytki1.d.jisi npo(phllaknikh MHrpeHH. Y )J,eTei:t B KJIIIHIILiecKIIX uccne.d.obahi1six TonaMaKc noctenehho OTMeH.SIJII1 B TeLieHHe 2-8 He)J,eJib. Ecnu no Me.D.11U11HCKI1M noka3ahi1.sim Heo6xo.nuMa 6biCTpaSI OTMeHa npenapata TonaMaKc, TO pekomeh.d.y; TC.SI ocymectbji.sitb COOTBeTCTB.)'IOU(HH KOHTpOJib COCTO.SIHHSI nauhehta. KaK 11 B cnyliae nphmehehh.si.npyr11x npotiib03ilhjienthlieckiix npenapatob, y HeKoTopbiX nau11ehtob, npiihhmaiou(iix TOnHpaMaT, Ha6JIIO)J,aeTC.SI nobbiwehhe LiaCTOTbl npuna,d.kob HJIH HOBbie Hlnbl npuna)j,kob. ):(ahhoe SIBJieHHe MOJKeT SIBJI.SITbC.SI nocjie)j,ctbhem nepe.d.0311pobki1, CHHJKeHH.SI KOHUeHTpaUHH COBMeCTHO nphmeh.si~mbix npohib03n11jiellti1lieckhx npenapatob, nporpecchpobamisi Ja6onesaHH.SI HJIH napa.nokcajibhoro 3cpcpeKTa. CKopocTb BbiBe)J,eHH.SI Liepe3 nolikh 3aBI1CHT OT cpyhku1111 IlOLieK II He 3aBHCHT OT B03pacTa. Y 60JibHbiX C ymepehhbim Hml Bbipa)J(eHHblM HapyweHI1eM cpyhkuhh noliek )J,JI.SI )J,OCTmKeHHSI.)'CTOHLiliBbiX KOHUeHTpaUHH B njia3me MO)J(eT noha,d.0611tbcsi OT I 0 )],0 15,D.Hei:J, B OTJIHLIHe OT 4-8 )J,Hei:J y 60JibHbiX C HOpMaJibHOH cpyhkuheh noliek. KaK 11 nph JII06oM 3a6onesaHI111, cxema no.d.6opa.d.03bl.d.oji)j(ha op11ehthpobatbcsi Ha KJIIIHHLiecKI1H J (p(pekt (T.e., CTeneHb KOHTp01111pOBaHH.SI nphila)j,kob, OTC.)'TCTBHe no60lihbix 3cpcpeKTOB) H.)'LIHTbiBaTb TO, LITO y 60JibHbiX C HapyweHHeM cpyhku1111 noliek )J,JISI.)'CTaHOBJieHII.SI CTa611JibHOH KOHUeHTpaU~IH B nna3me.d.ji.si Ka)J()J,oi1.D.03bi MOJKeT noha.no611tbcsi 6onee npo.d.oji)j(i1tej1bhoe spem.si. np11 TepamiH TOniipaMaTOM B03MO)J(H0 B03HIIKHOBeHI1e OmifOrH)J,p03a (ymehbwehhoe notoot.d.ejieh11e) 11 ahm.d.p03a. YMeHbWeHI1e notoot.d.ejiehh.si 11 nmeptepmh.si (nobbiwehi1e Tel\mepaTypbl TeJia) MOryT B03HHKH.)'Tb y )J,eTeH, no,d.bep)j(ehhbix B03)J,eHCTBI1JO BbiCOKOH TeMnepaTypbl OKp.)'ii<UIOU(eH cpe)j,bl. 8 3TOll CBSI311 np11 TepamiH TOI111paMaTOM OLieHb Ba)J(HO a)j,ekbathoe IlOBbiWeHIIe o6bema notpe6jisie~ioh )KH.D.KOCTI1, cnoco6hoe CHII311Tb puck pa3bhti1.si HecppomiTIJa3a, a TaKil<e nooolihbix 3cpcpeKTOB, KOTOpbie MOf.)'T B03HI1KH.)'Tb 110)], B03,D.eHCTBI1eM cp113hlieckiix Harpy30K IIJIII nobbiwehhbix TeMneparyp. Paccmpoiicmea 1/QC111pOelll/Jll oenpeccl/jl np11 JieLieHIIII TOnllpaMaTOM Ha6JIIO)J,aeTCSI IlOBbiWeHHaSI LiaCTOTa B03HHKHOBeHH.SI pacctpohctb I IaCTpOeHI1.SI 11 )J,enpeCCHH. Cymfu(Jcuibllbie nonbll11h"ll npl1 npumehehhh npothb03nhjienthlieckhx npenapatob, BKJIIOLia.SI npenapat TonaMaKc, ysemilihbaetcsi phck nosibjiehh.si cym.jji.d.ajibhbix MbiCJiei:t H cyihj,h.d.ajibhoro nose.nehh.si y nauuehtob, nphhiimaiow,hx 3TH npenapatbl no JII06biM 113 noka3ahhh. 14

15 .UBOHHblX CJJenbiX KJIHHHlfeCKHX HCCJJe.UOBaHWIX <JaCTOTa pa3bi1ti1.r.rbjjehhh, CBSI3aHHbiX C 8 cyhuh.uom ( cyuuh.uajjbhbje MbJCJlH, nonbjtkh cyuu11.ua, cy11uh.u), coctasn.rna 0,5% y nauuehtob, nojlylfabwhx TOnllpaMaT (y 46 lfejjobek U3 8652), lfto nphmepho B 3 pa3a BbJWe no cpabhehiuo C nauhehtamh, nonylfabwhmh nnaue6o (0,2%; y 8 lfenosek m 4045). 0.UHH cjjylfah cyuuu.ua 6bJJJ JacpHKCHpOBaH B.UBOHHOM CJJenOM 11CCJJe.UOBaHI111 6HnOJl.RpHOfO pacctpoi:fctba y nauhehta, nonyyaswero TonupaMaT. TaKHM o6pa30m, He06XO.U11MO KOHTpOI111pOBaTb COCTO.RHHe nauhehtob C UeJJbiO Bbi.RBJJeHH.R np113hakob cyhuh.uajjbhbix MbiCJJefi 11 Ha3Ha JaTb cootbetctbyjotuee nelfehhe. Heo6xo.UHMO pekomeh.uobatb nau 11 ehtam (11 nph Heo6xo.uHMOCTH JJHUaM, yxajintbajotuhm 3a nauuehtamu) cpa3y ike o6pamatbc.r 3a Me.UHUHHCKOH nomolubio B CJJylfae no.rbjjehh.r nph3hakob CYIIUH.UaJJbHbiX MbiCJJeH IIJIH cyhuh.uajjbhofo nose,uehh.r. HerjJpommwm y HeKOTOpblX 6oJJbHbiX, B oco6ehhocnj, c npe.upacnojjo)f(ehhoctbjo K HecppomJTHa3y, MmKeT nobbichtbc.r phck o6pa30bahj1jj KaMHeH B nolfkax II nosibjjehhsi CB.R3aHHbiX C HIIM C~JMnTOMOB, TaKHX KaK nolfelfha.r KOJIIJKa, 60JJb B nolfke, 60JJb 8 6oKy. 4T06bJ ymehbwiitb 3TOT phck, He06XO.UHMO a,nekbathoe nobbjwehhe 06beMa notpe6jl.remoh )f(h,ukochi. <l>aktopamh p11cka pa3bhth.r HecppOI111THa3a.RBJI.RIOTC.R HecppOI111TI1a3 B ahamhe3e (B T.lf. B CeMeHHOM), nmepkajjbuhyph.r, conytctbyjoll.i,a.r TepamJ.R npenapatai\hj, KOTOpble cnoco6ctbyiot pa3bhhiio HecppOI1HHJa3a. Hapyzueuue rjjym;:lfllll 110L{eK Cne.uyeT co6jjjo.uatb octopo)f(hoctb IJPH Ha3HalfeHHI1 npenapata TonaMaKc nauhehtam c nolfelfhoh He.UOCT8TOlfHOCTbiO (KIIHpeHC KpeanJHIJHa <70 MJJ/MHH). JTO CB.R3aHO C TeM, lfto y TaKHX nauj1ehtob KIJIIpeHc npenapata nohj1ji<eh. Hapyweuue rjjym;:lfllll ne'leuu Y nauuehtob C HapyweHHSIMH cpyhkuhi1 nelfehj1 TOnHpaMaT CJJe,nyeT nphmeh.rtb C OCTOpO)f(HOCTbiO 113-Ja B03MO)f(Horo CHH)f(eHJI.R KIJllpeHca 3Toro npenapata. Nfl/0/11/Jl p11L{11QR 3ahpbli110_W~O/lb11QR i'.'iq)'k"o.\iq np11 np11mehehhi1 npenapata TonaMaKc OnJJCaH CHH.UpOM, BKJIJOlfaJOLL.I,HH OCTPYIO MIJOnHJO c ConyTCTBYJOLL.I,eH BTOpHlfHOH 3aKpblTOYfOJibHOH rjjaykomoh. CuMnTOMbl BKJ110lf810T OCTpoe CHH)f(eHHe OCTpOTbl 3peHII.R ~Jft1JJH 60Jlb B fjja3y. np11 OcpTaJJbMOJIOrHlfeCKOM 06CJJe.UOB8HI111 MOJI<eT o6hapy)f(hbatbcsj MHOnH.R, ynnowehhe nepe.uhei:f KaMepbl rna3a, nmepemh.r (nokpachehue) rna3horo.rojjoka, nobbjwehue BHyTpHrJJa3Horo.uasJJeHJ1.R. Mo)f(eT Ha6JlJO.UaTbC.R MH.Uplla3. 3TOT CI1H.UpoM MO)f(eT conpobo)f(,uatbc.r CeKpeul1efi )f(j1,ukocti1, npiibo.u.rll.i,eh K CMell..l,eHHIO XpyCTaJJIIKa 11 pa.uy)f(hoh o6ojjolfki1 snepe.u c pa3bhnlem BTOplllfHOH JaKpbJToyroJJbHOfi maykombj. CuMnTOMbl o6bjlfho nosjbjjhjotc.r Yepe3 I MeCHU nocne HalfaJJa npumehehhsi npenapata TonaMaKc. 8 otjjillfhe ot nepbillfhoh OTKpbiTOyrOJJbHOH rjjaykombl, KOTOpa.R pe.uko Ha6JlJO,UaeTCH y 60JJbHbiX.UO 40 JleT, BTOplllfH8Sl 3aKpb1TOYrDJJbHaSI rjjaykoma Ha6JJJO,UaeTCH np11 npl-jmehehj111 TOnHpaMaTa KaK y B3pOCJlbiX, TaK 11 y,ueteh. npu 803HI1KHOBeHIHI CHH.UpOMa, BKJIJOlfaJOLL.I,ero 1\HIOnlliO, CBSI3aHHYIO C JaKpbJToyroJJbHOfi rnaykomoh, JJelfeHile BKIJJOlfaeT npekpamehj-je nphema npenapata TonaMaKc, KaK TOJlbKO Jlelfall..I,HH spay COlfTeT 3TO B03MOii<HbiM, 11 COOTBeTCTByJOLL.I,~Je Mepbl, HanpaBJJeHHbJe Ha nohmkehhe BHyTpumaJHoro.uasneHIIH. 06bJ JHO 3TH Mepbl nphbo.u.rt K HOpMaJJHJauuu BHyTpurnaJHoro nasnehh.r. 15

16 llobbiwehhoe BHYTPitr11a3Hoe.nas11eH11e mo6oi1 3TH0110riii1 np11 OTCYTCTBHI1 a.nekbathoro 11e1.JeHHH MO)KeT np11bectii K cepbe3hbim OC110)KHeHHSIM, Bn110Tb AO noteph 3peHIISI.!lpH Ha 3 HaLJeHHI1 TOmtpaMaTa nau,l1ehtam C 3a6011eBaHI1SIMH rna3 B ahamhe3e He06XOAHMO OLI,emtTb OTHOWeHHe omhaaemoh n011b3bl K B03MO)KHOMY phcky nphmehehhsi. /(epe~-:mbl no_rm 3peHUR }J;ecj>eKTbl n011si 3peHI ISI Ha61110Aa1111Cb y nali,hehtob, np11hi1maioi.l.uix TOnHpaMaT, He3aBHCHMO OT Ha11I11.JHSI y HI1X nobbiwehhoro BHyTp11r11a:moro AaB11eHHSI. 8 XOAe KJlHHHI.JeCKHX 11CC11eAOBaHHH 6o 11 bwhhctbo TaKHX c11yljaes HMemt o6panimbih xapaktep, 11.necj>eKTbl no11h 3peHHH HCLJe3a1111 noc11e OTMeHbl TepamiH TOn11paMaTOM. llph B03HI1KHOBeHlJH npo6jiem CO 3peHHeM 80 BpeMSI nphema TOnl1paMaTa, C11e.nyeT paccmotpetb B03M0)KHOCTb npekpamehwi TepamtH.!vfema6o:7U'leCKuii GlfU003!lpH np11mehehi111 TOmtpaMaTa MOmeT B03HHKaTb ntnepxnopemhi.jeckhh, He CBSI3aHHbiH C.necj>HI..(HTOM ahhohob, MeTa6omtLJeCKHH ali,ha03 (HanpHMep, CHHmeHHe KOHLI,eHTpau,HH ntapokap6ohatob B n11a3me HH)Ke HOpMa11bHOrO ypobhsi nph OTCYTCTBHH pecmtpatophoro a11ka1103a). ilo.!j,06hoe CHI1)KeHHe KOHLI,eHTpaLI,HI1 rhapokap6ohatob CbiBOpOTKH KpOBH SIB11SieTCSI CJieACTBHeM HHr116~1py10mero 3cj>cj>eKTa TOmlpaMaTa Ha noljeljhyio Kap60UHrHApa3y bWHHCTBe C11yLJaes, CHI1meHIIe KOHLI,eHTpaLI,I111 ri1apokap6ohatob npmtcxoaht B HaLJane np11ema npenapata, XOTSI AaHHbiH 3lpcj>eKT MOmeT nposibi1tbcsi s mo6om nepuo.ne 11e1.JeHHH TOn11paMaTOM. CTeneHb CHumemm KOHLI,eHTpau,I1H o6biljho c11a6ah ymepehhasi (cpeahee 3HaLJeHHe COCTaB11HeT 4 MM011b/11 nph HCnOJib30BaHHH y B3pOC11biX nau,hehtob B,!J,03e BbiWe I 00 Mr B AeHb H OKQJlO 6 Mr B AeHb Ha Kr MaCChi Te11a np11 HCn011b30BaHIIH B nea11atphljeckoh npaktiike). 8 peakhx C11yLJaSIX y nau,hehtob OTMei.Ja110Cb CHI1meHHe KOHLI,eHTpaLI,IHI m.npokap6ohatos HHme ypobhjj I 0 MM011b/JI. HeKoTopble 3a6o11esaHHSI cnoco6bl 11eLJeHHSI, npe.npacno11ara10m11e K pa3bhtiiio au,ha03a (HanpHMep, 3a6o11esaHHH noljek, TSime11ble pecn11patophbie 3a6o11eBaHitll, 3nHJienntLJeCKHH ctatyc, AHapeH, xupypmljeckhe BMewaTe11bCTBa, KeToreHHaSI AHeTa, npuem HeKOTOpbiX 11eKapcTBeHHbiX npenapatos) MOryT ObiTb.nono11HHTe11bHbiMH cj>aktopamh, ycummajomiimi1 ru.npokap6ohat-chhmajomhi1 3cj>cj>eKT TonHpaMaTa. Y,!J,eTeH XpOHHLJeCKHH MeTa60J1111.JeCKHH ali,11a03 MOmeT nphboahtb K 3aMeAJ1eHHIO pocta. 3cj>cj>eKT TOnHpaMaTa Ha poet H B03MO)KHbie OCJIO)KHeHHSI, CBH3aHHble C KOCTHOH CIICTeMOH, He 113YI.Ja1111Cb CHCTeMaTH'IeCKI1 y AeTeH 11 y B3pOC11biX. 8 CBll311 C BbiWei13110)KeHHbiM, np11 11eLJeHI111 TOnHpaMaTOM pekomehayetcll npoboahtb He06XOA11Mbie HCC11eAOBaHHll, BKJliOLJall onpe.ne11eh11e KOHLI,eHTpaLI,HI1 ntapokap6ohatob B CbiBOpOTKe. 8 CJiyLJae nol!b11ehiisi cumntomob MeTa6omtLJecKoro au,ha03a (HanpHMep, r11y6okoe KyccMay11eBcKoe JJ.biXaHHe,,!l,I1CnH03, UHOpeKCHSI, TOWHOTa, pbota, nobbiwehhall YTOM11HeMOCTb, TaXIIKapJJ.IISI IIJIH aphtmilsi) pekomehayetcll npobejj,ehhe onpeae11ehiisi KOHLI,eHTpaLI,I1H fhapokap6miatob B CbiBOpOTKe. ilph B03HIIKHOBeHIUI MeTa601111LJeCKOfO ali,ha03a II ero nepchcti1pobahiii1, pekomehayetcll CHI1311Tb A03Y npekpanitb nphem TonupaMaTa. Hapyweuue,.;ozHII111U6HblX rfjyii"-"l{llii HapyweHue KOrHHTI1BHbiX cj>yhkli,hh np11 3nH11enCHI1 HMeeT MHOrocj>aKTOpHyiO nphpoay, II MO)KeT ObiTb Bbi3BaHo nepsonphljhhoh 3a6onesaHWI, IlenocpeJJ.CTBeHHO 3n1111encHei npotiib03ni1jienthi.jeckoh Tepanuefi. Y B3pOC11biX nau,hehtob, nphh11maioi.l.(hx TOmtpaMaT, OTMei.Ja11HCb C 11 Y'IaH HapyWeHHji KOfHIITHBHbiX q>yhkli,hh, Tpe6osaBWI1e CHH)KeHHll JJ,03bl npekpal.l.leh~m Tepamm. }J;aHHbie no B1111SIHHIO TOmtpaMaTa Ha KOrHIITHBHble lpyhkli,ihi y JJ,eTefi HeJJ,OCTaTO'IHbl, 11 ero 3 li>q>ektbl Tpe6yiOT Aa11bHeHwero 113Y'IeHIISI. 16