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59 2023-03-18
ϺF(xin)fƽƬôϺF(xin)fƽƬôʹt(y)ˎW(wng)ѼP(gun)ϺF(xin)fƽƬf,ϺF(xin)fƽƬr(ji),ϺF(xin)fƽƬX,ϺF(xin)fƽƬĹЧc,ϺF(xin)fƽƬ÷cˎƷϢȫԃʹ
ƷQ:ϺF(xin)fƽƬ
(zhn)̖(ho):ˎ(zhn)4085200H4
:fƽcD(zhun)䛲ˎίHIV-1Ⱦôˎ(hu)ܿa(chn)ˎfƽ(yng)cكɷNϵD(zhun)䛲ˎһʹ(du)ڷr(sh)δʹÿD(zhun)䛲ίЋD(yng)fƽ(ԲcD(zhun)䛲ˎ)A(y)HIV-1ĸЋDr(sh)ֻڷ΄fƽڳֻڷ΄fƽ(Ҋ÷;2RоC)еԒha(chn)Dڮa(chn)ǰfƽcD(zhun)䛲ˎpHIV-1ĸęC(j)
÷:1.˻ߣʮfƽ]ÿһƬÿƬ200mg(@һ(do)ڵđ(yng)ÿԽƤl(f))(do)ں÷ÿՃɴÿһƬͬr(sh)ʹكɷNϵD(zhun)䛲ˎ(du)Щˎ(yng)ѭSҵ]ґ(yng)(du)@ЩˎM(jn)бO(jin)2.ͯߣ(du)ڃɂ(g)µ˚qăͯfƽĿڷ]ˎʼܰ4mg/kgһһνoˎ֮7mg/kgһɴνoˎ(du)ڰ˚qͰ˚qϵăͯ]ʼܰ4mg/kgһһ֮4mg/kgһɴκλÿˎó^400mg3.A(y)HIVĸ(du)ڌRϷЋDfƽ]£ĸH÷ڷ_ʼMܵؿڷ΄200mg÷ڳ72Сr(sh)(ni)2mg/kg΄ڷˎa(chn)Dڮa(chn)냺ǰСr(sh)(ni)õfƽô(yng)2mg/kg΄ڷfƽһηˎ2472Сr(sh)(ni)2mg/kgٷһfƽ(yng)֪߰̎ÿշfƽıҪԡ©ˎߑ(yng)ԓMһˎҪӱڑ(yng)fƽǰˎgm(dng)g(yng)M(jn)Rz飬ιܙz(Ҋע(xing))ˎgF(xin)(yn)ƤSȫYƤ(yng)ԓͣˎڌ(do)ʮ(ni)200mg/r(sh)F(xin)ƤtߵˎֱƤʧ(Ҋע(xing))߳F(xin)жȻضȸιܮ(GGT)(yng)ֹͣʹfƽֱιܻ֏(f)A(ch)ˮƽ֮fƽ(yng)200mg/_ʼoˎM(jn)һ^Ȼ֔(jn)ӄ200mg/ÿՃɴΡٴγF(xin)жȻضȸιܮfƽ(yng)ԓͣˎ(Ҋע(xing))ͣfƽ^(yng)սoˎԭt_ʼ200mgˎÿһΌ(do)֮ÿ200mgÿնΡ
ͨQ
fƽƬ
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?fƽcD(zhun)䛲ˎίHIV-1Ⱦôˎ(hu)ܿa(chn)ˎˣfƽ(yng)cكɷNϵD(zhun)䛲ˎһʹ
(du)ڷr(sh)δʹÿD(zhun)䛲ίЋD(yng)fƽ(ԲcD(zhun)䛲ˎ)A(y)HIV-1ĸЋDr(sh)ֻڷ΄fƽڳֻڷ΄fƽ(Ҋ÷;2RоC)еԒha(chn)Dڮa(chn)ǰfƽcD(zhun)䛲ˎpHIV-1ĸęC(j)
÷
1.˻ߣʮfƽ]ÿһƬÿƬ200mg(@һ(do)ڵđ(yng)ÿԽƤl(f))(do)ں÷ÿՃɴÿһƬͬr(sh)ʹكɷNϵD(zhun)䛲ˎ(du)Щˎ(yng)ѭSҵ]ґ(yng)(du)@ЩˎM(jn)бO(jin)
2.ͯߣ(du)ڃɂ(g)µ˚qăͯfƽĿڷ]ˎʼܰ4mg/kgһһνoˎ֮7mg/kgһɴνoˎ(du)ڰ˚qͰ˚qϵăͯ]ʼܰ4mg/kgһһ֮4mg/kgһɴΡκλÿˎó^400mg
3.A(y)HIVĸ(du)ڌRϷЋDfƽ]£
ĸH÷ڷ_ʼMܵؿڷ΄200mg
÷ڳ72Сr(sh)(ni)2mg/kg΄ڷˎa(chn)Dڮa(chn)냺ǰСr(sh)(ni)õfƽô(yng)2mg/kg΄ڷfƽһηˎ2472Сr(sh)(ni)2mg/kgٷһfƽ
(yng)֪߰̎ÿշfƽıҪԡ©ˎߑ(yng)ԓMһˎҪӱá
ڑ(yng)fƽǰˎgm(dng)g(yng)M(jn)Rzιܙz(Ҋע(xing))
ˎgF(xin)(yn)ƤSȫYƤ(yng)ԓͣˎڌ(do)ʮ(ni)200mg/r(sh)F(xin)ƤtߵˎӣֱƤʧ(Ҋע(xing))
߳F(xin)жȻضȸιܮ(GGT)(yng)ֹͣʹfƽֱιܻ֏(f)A(ch)ˮƽ֮fƽ(yng)200mg/_ʼoˎM(jn)һ^Ȼ֔(jn)ӄ200mg/ÿՃɴΡٴγF(xin)жȻضȸιܮfƽ(yng)ԓͣˎ(Ҋע(xing))
ͣfƽ^(yng)սoˎԭt_ʼ200mgˎÿһΌ(do)룬֮ÿ200mgÿն
(yng)
ˣ
Ƥι⣬Rԇ(yn)cfƽίP(gun)ҊIJ(yng)Аƣl(f)^ʹ˯IaʹͼʹdzٵĎؚѪѪpٰYcfƽίP(gun)fƽίĻP(gun)(ji)ʹĂ(g)(bo)
кr(yn)صˎﲻ(yng)Stevens-JohnsonCԱƤxذY/˥ߺ^(yng)ƤȫYl(f)P(gun)(ji)ʹʹܰͽY(ji)Լ(ni)KpἚ(x)ࡢ(x)ȱYIܓpʼ812ܵίǺP(gun)IAM(jn)Ҫ(yn)ܱO(jin)y(Ҋע(xing))
ƤwƤ½M
fƽҊRLJ(yn)Ƥ{Ƥw(yng)Stevens-JohnsonC(SJS)ͺҊĶԱƤx(TEN)fƽίĻߴs2%(hu)F(xin)Y
ɣ
1.(du)fƽĻԳɷߴˮa(chn)Ʒκx΄R@^(yng)Ļfƽ(yng)
2.(du)ڇ(yn)ƤƤȫY^(yng)fƽĸДfƽίĻ߲·
3.ڷfƽg^F(xin)ASATALAT>ֵ5(yng)fƽѸُ(f)l(f)ιĻߑ(yng)(Ҋע(xing))
ע(xing)
Ʒί8ǺP(gun)IA(du)rM(jn)Ї(yn)ܵıO(jin)yr(sh)l(f)F(xin)ڵć(yn)غ{Ƥw(yng)(yn)صĸ/˥횇(yn)Ҫ14쌧(do)ڕr(sh)(du)ڱO(jin)ylʣЌָÿһeӄ֮ǰӺ2
(du)KӰ푣
fƽίĻF(xin)(yn)صġĸKԼđ֭ٷeԸסΉ(yn)صĸKl(f)ίǰ12܃(ni)һЩ^tF(xin)
ͨڿί_ʼr(sh)ͳF(xin)ALTASTˮƽtίgKl(f)¼ΣU(xin)Ծ(yng)fƽί
(yng)֪fƽҪĶnj(du)Kˎ8܃(ni)(yng)^ԓãO(jin)yALTASTˮƽˎgЪgҲ(yng)O(jin)yιܡ
(yng)֪F(xin)ǰ(q)Y(yng)t(y)
Ƥw(yng)
(yng)fƽίĻF(xin)(yn)صļƤw(yng)ʷ˹sdCƤжԉܽYƤȫYٹɁyĸ(yng)߳F(xin)Ϊ(d)Ƥ(yng)(yn)^(du)ڮa(chn)(yn)ƤSȫY(l(f)ˮ[P(gun)(ji)ʹˮǻpY(ji)Ĥȫm)Ƥʷ˹sdCƤжԉܽYĻߑ(yng)ͣˎM(jn)Йz(du)ȫYĸ(yng)Ƥ(x)(x)ȱIϵK(ni)KܓpEͣˎ
(yng)֪ƤDZƷҪ֮һ?q)ڿԽƤİl(f)ʴADZҪڌ(do)ʮ(ni)F(xin)ƤtߵˎֱƤʧ
fƽίǰ14(ni)ͬr(sh)Ï(qing)(40mg/)ܽcfƽP(gun)Ƥڷfƽ6܃(ni)Ƥİl(f)
DŮfƽٲÿڷˎطM(jn)бС
ߑ(yng)֪Ʒίδ@ʾɜpHIV-1Ⱦo˵ΣU(xin)
ƷHIV-1Ⱦ߿^m(x)F(xin)̲l(f)YC(j)(hu)ԸȾt(y)O(jin)o(h)ί
һҪ̎ÿˎδ(jng)t(y)S{(dio)©ˎ(yng)Mһˎo횼ӱfƽҪɸKxIM(jn)дx˸ΡI˥ˎr(sh)Ҫeע
(dng)fƽ鿹D(zhun)øwϵһ֕r(sh)_ʼˎǰ(yng)(du)ÿһɷ˽⡣
ɷݣ
fƽ
Ԡ
ƷɫɫƬ
ˎã
fƽǸμ(x)ɫP450xø(CYP3ACYP2B)T(do)ҪCYP3ACYP2BxˎcfƽÕr(sh)fƽԽ@ЩˎѪ{(Ҋˎx(dng)W(xu))һ(g)ڽCYP3ACYP2Bxˎһ(g)(wn)ί_ʼfƽǰˎҪ{(dio)
D(zhun)øƄ
(dng)fƽcB(zidovudine)didanosinezalcitabineÕr(sh){(dio)@ЩˎĄăɽMԯB(zidovudine)ί鱳ίо(n=33)ɵõB(zidovudine)ľCϔ(sh)(j)HIV-1ȾĻ߆Ϊ(d)fƽ(400mg/)ίfƽdidanosine(200300mg/)fƽzalcitabine(0.3750.75mg/)ίԇ(yn)Y(ji)fƽ(du)Bˎr(sh)e(AUC)½o@13%;(du)BCmaxo@5.8%B(zidovudine)(du)fƽˎ(dng)W(xu)oӰһоfƽ(du)didonosine(n=18)zalcitabine(n=8)ķ(wn)B(ti)ˎ(dng)W(xu)oӰ
(du)25HIVȾĻ(yng)fƽnelfinavir(70mgtid)stauvdine(30-40mgbid)ί36Rԇ(yn)Y(ji)@ʾstauvdineAUCCmaxoy(tng)Ӌ(j)W(xu)@׃(du)90lamivudinefƽһMfƽӰοίĻM(jn)Ⱥˎ(dng)W(xu)оY(ji)@ʾlamivudine^ʺͷֲݷeo׃@fƽ(du)lamivudineoӰ
ǺD(zhun)øƄRԇ(yn)(14)Y(ji)@ʾfƽcefavirenzòӰfƽ(wn)B(ti)ˎ(dng)W(xu)(sh)efavirenzcfƽˎ@½efavirenzAUC½22%Cmax½36%cfƽҪCefavirenzÿӵ800mg
øƄԇ(yn)Уfƽˎ200mgÿһܡ֮200mgÿՃɴ28졣
Saqinavirһ(xing)Rԇ(yn)(31)HIVȾĻ߷fƽsaqinavir(Ӳzң600mgÿ)Y(ji)ߺÌ(do)saqinavirAUCƽ½24%(P=0.041)fƽѪ{ȟo@׃(do)saqinavirӲzAUC½M(jn)һsaqinavirѪ{½õRxв(lin)ˎӰfƽˎ(dng)W(xu)
һ(xing)Rԇ(yn)(20)оÿһηsaqinavirܛzҺ100mgritonavirеĻ߶ͬr(sh)fƽоY(ji)cvʷ(du)saqinavirܛzҺ100mgritonaviròӰfƽˎ(dng)W(xu)(sh)saqinavirܛzҺ100mgritonavirÌ(du)fƽˎ(dng)W(xu)ӰRϛ]@ԡ
Ritonavir(dng)fƽcritonavirÕr(sh){(dio)Rԇ(yn)(n=25)HIVȾͬr(sh)nevirapineritonavir(600mgÿՃɴÄuˎ)ίѪ{Ⱦo@׃
IndinavirRԇ(yn)(n=25)HIVȾ߽fƽindinavir(800mg8Сr(sh)һ)ίindinavirAUCƽ½28%(P<0.01)fƽѪ{ȟo@׃(du)fƽindinavirõĝӰ߀]п϶RY(ji)ՓfƽcindinavirÕr(sh)(dng)fƽ200mgÿՃɴΕr(sh)indinavirɿ]ӵ1000mgÿСr(sh)һĿǰПoY@ʾoindinavir1000mgÿСr(sh)һfƽ200mgÿՃɴcindinavir800mgÿСr(sh)һfƽ200mgÿՃɴΣɷĶڻLڿкβͬ
Nelfinavirһ(xing)36Rԇ(yn)(n=25)(yng)fƽnelfinavir(75mgÿ)d4T(3040mgÿն)HIVȾߣںfƽnelfinavirˎ(dng)W(xu)(sh)]нy(tng)Ӌ(j)W(xu)@׃(AUC+4%Cmax+14%Cmin-2%)cǰYfƽˎˮƽo׃
(dng)fƽcκεøƄÕr(sh)ПoȫԽ͵Ĉ(bo)
ڽ־Ըкlopinavirfƽlopinavirˎ(dng)W(xu)(sh)]аl(f)F(xin)@׃
ڽ(jng)^øƄΪ(d)ίĻfƽlopinavirritonavir400/100mg(3(g)z)һɴԼD(zhun)øƄãķ(yng)ʷdz
ƻˎ(dng)W(xu)оY(ji)@ʾlopinavircfƽÕr(sh)Ƚ͡F(xin)߀֪@NRǷ@(dng)cfƽÕr(sh)(yng)]lopinavir/ritonavir533/133mg(4(g)zһ6.5ml)?yn)Rϑɽˌ(du)lopinavir/ritonavir(Rί͌(sh)(yn)Ҕ(sh)(j)C)
ͪ(Ketoconazole)fƽ200mgÿնͪ400mgÿһκÕr(sh)P(gun)ͪˎ(dng)W(xu)(sh)@(AUCƽ½63%Cmaxƽ½40%)ͬһԇ(yn)cǰYͪ(Ketoconazole)ʹfƽѪ{ˮƽ1528%ͪfƽ(yng)ϲˎfƽ(du)(itraconazole)ӰвmȻПoˎõԇ(yn)IKйĿˎ()ɴͪ
CYPͬøT(do)
ƽһ(g)_о(n=14)fƽ(du)ƽķ(wn)B(ti)ˎ(dng)W(xu)(sh)CmaxAUCo@Ӱ෴ͬǰYƽ@fƽAUC(-58%)Cmax(-50%)Cmin(-68%)(dng)fƽƽÕr(sh)ĿǰПoYό(du)脩{(dio)M(jn)u(png)
fƽ200mgb.i.d.300mgq.d(ͬr(sh)ZDVøƄί150mgq.d)Y(ji)@ʾĝț]@׃(AUCƽ12%Cminssƽ½3%)Cmaxss@(20%)Դxa(chn)25-O-desacety-lĝț]@׃ͬӵоУͬǰYʹfƽϵy(tng)@(9%)@Щ׃oҪRxͬr(sh)fƽǰȫģҪ{(dio)
]ͬr(sh)fƽSt.JohnswortSt.JohnswortĮa(chn)Ʒ?yn)Ј?bo)@ʾSt.Johnswortˎ֮gáSt.Johnswortͬr(sh)÷ǺշD(zhun)øƄfƽɽͷǺշD(zhun)øƄĝӰfƽˎЧʧȥãʹa(chn)(du)fƽǺD(zhun)øƄˎ
CYPͬøƄfƽͿùصˎоY(ji)ˎÕr(sh)ùصAUC(-30%)Cmax(-21%)Cmin(-46%)@ùصĻԴx14-OHùصAUC(58%)Cmax(62%)@ߡfƽCmin(28%)@AUC(26%)Cmax(24%)@@ЩY(ji)ʾ(dng)ˎÕr(sh)ˎĄ{(dio)
ڌ(du)fƽRԇ(yn)ߵāȺܼ(Cimetidine)(n=13)ίĻߣfƽķ(wn)B(ti)ֵѪ{(7%)
ڷˎfƽ200mgb.i.d.c΄0.035mgȲƶ(EE)1.0mgȲZͪ(Ortho-Novum?1/35)Ŀڷˎͬr(sh)Õr(sh)cǰΪ(d)fƽѪ{ȱ^28fƽ17?-EEAUC@½(29%)EEƽںͰ˥@sȲZͪƽAUC@(18%)ƽںͰ˥ڛ]и׃ϲ(yng)fƽڷˎĄ܉{(dio)(du)m(yng)Yί(ӌm(ni)ĤλY)úдƼ/ͪĿڷˎܱܿʧ(du)ڷfƽпċDŮhʹʽ(ˎ߱)߿ڷˎ{(dio)(ji)ˮƽr(sh)Ϸfƽ(yng)(du)ǰM(jn)бO(jin)y
Yϣ
˵ĸμ(x)wwоfƽuxa(chn)γɲܰ(dapsone)ƽS/ǰӰ푡ͪͼtùؿ@fƽuxa(chn)γПoP(gun)Rԇ(yn)
(yng)ע(dng)cfƽÕr(sh)CYP3ACYP2B6ĵˎѪ{ȿ½ڌ(du)ɳͪxC(j)Ƶ˽⣬fƽͨ^ӸδxܽɳͪѪ{(j)(bo)ͬr(sh)(yng)fƽɳͪίĻF(xin)CɳͪSֽoˎIJ˺fƽr(sh)hм(x)^C(du)ɳͪĄM(jn)(yng){(dio)
ˎã
ÙC(j)ƣ
fƽwȱݲHIV-1ķǺD(zhun)øƄNNRTIfƽcHIV-1D(zhun)øֱӽY(ji)ϣͨ^ƉԓøĴλc(din)RNAهDNAهDNAۺøĻfƽcծa(chn)fƽ(du)HIV-2D(zhun)ø˼(x)DNAۺø(DNAۺø¡û)o
wԣwHIV-1(du)fƽcw(ni)fƽHIV-1(f)P(gun)δ_fƽw⿹ͨ^Ѫκ˼(x)ɼ(x)ܰͼ(x)y䌦(du)(sh)(yn)ҼRxHIV-1IC50딵(sh)Ɲȣ10-100nM(x)B(yng)ԇ(yn)ʾfƽcRȥu˾ɳff(lin)ί(du)HIV-1Ѕf(xi)ͬ
ˎԣ
wԇ(yn)зxˌ(du)fƽԽ100-250HIV-1@ʾͻ׃F(xin)HIV-1D(zhun)øϵĵ181/106λλc(din)
ˎԣwѰl(f)F(xin)(du)ǺD(zhun)øƄˎٳF(xin)HIVP(gun)ڷǺD(zhun)øƄfƽcD(zhun)øƄĽˎԔ(sh)(j)߀4(g)wyRˎxꌦ(du)fƽ6(g)wyfƽˎxꌦ(du)RȥuվԡøIJͬfƽcHIVøƄF(xin)ˎԵĿԲ
ϺF(xin)ɭ h(hun)ô,ϺF(xin)ɭ h(hun)ôʹt(y)ˎW(wng)ˎƷlṩϺF(xin)ɭ h(hun)f,ϺF(xin)ɭ h(hun)r(ji),ϺF(xin)ɭ h(hun)X,ϺF(xin)ɭ h(hun)...
ϺF(xin)ɭ ̩ô,ϺF(xin)ɭ ̩ôʹt(y)ˎW(wng)ˎƷlṩϺF(xin)ɭ ̩f,ϺF(xin)ɭ ̩Ƀr(ji),ϺF(xin)ɭ ̩ɶX,ϺF(xin)ɭ ̩ɵĹЧc...
ϺF(xin)ɭ ̹ô,ϺF(xin)ɭ ̹ôʹt(y)ˎW(wng)ˎƷlṩϺF(xin)ɭ ̹f,ϺF(xin)ɭ ̹r(ji),ϺF(xin)ɭ ̹X,ϺF(xin)ɭ ...
ϺF(xin)ɭ uAô,ϺF(xin)ɭ uAôʹt(y)ˎW(wng)ˎƷlṩϺF(xin)ɭ uAf,ϺF(xin)ɭ uAr(ji),ϺF(xin)ɭ uAX,ϺF(xin)...
ϺF(xin) L(fng)ɰلô,ϺF(xin) L(fng)ɰلôʹt(y)ˎW(wng)ˎƷlṩϺF(xin) L(fng)ɰلf,ϺF(xin) L(fng)ɰلr(ji),ϺF(xin) L(fng)ɰلX,ϺF(xin) L(fng)ɰلĹЧc...
ˎI(y) עҺô,ˎI(y) עҺôʹt(y)ˎW(wng)ˎƷlṩˎI(y) עҺf,ˎI(y) עҺr(ji),ˎI(y) עҺX,ˎI(y) ע...
Fݿƕ zô,Fݿƕ zôʹt(y)ˎW(wng)ˎƷlṩFݿƕ zf,Fݿƕ z҃r(ji),Fݿƕ zҶX,Fݿƕ z...