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59 2023-03-18
ϺF(xin)fƽƬôϺF(xin)fƽƬôʹt(y)ˎW(wng)ѼP(gun)ϺF(xin)fƽƬf(shu)(sh),ϺF(xin)fƽƬr(ji),ϺF(xin)fƽƬX(qin),ϺF(xin)fƽƬĹЧc,ϺF(xin)fƽƬ÷cˎƷϢȫԃʹ
ƷQ:ϺF(xin)fƽƬ
(zhn)̖(ho):(gu)ˎ(zhn)4085200H4
:fƽcD(zhun)䛲ˎίHIV-1Ⱦôˎ(hu)ܿa(chn)ˎfƽ(yng)cكɷNϵD(zhun)䛲ˎһʹá(du)ڷr(sh)δʹÿD(zhun)䛲ίЋD(yng)fƽ(ԲcD(zhun)䛲ˎ)A(y)HIV-1ĸЋDr(sh)ֻڷ΄fƽڳֻڷ΄fƽ(Ҋ(jin)÷;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^(gu)400mg3.A(y)HIVĸ(du)ڌRϷЋDfƽ]£ĸH÷ڷ_(ki)ʼMܵؿڷ΄200mg÷ڳ72Сr(sh)(ni)2mg/kg΄ڷˎa(chn)Dڮa(chn)냺ǰСr(sh)(ni)õfƽô(yng)2mg/kg΄ڷfƽһηˎ2472Сr(sh)(ni)2mg/kgٷһfƽ(yng)֪߰̎ÿշfƽıҪ©ˎߑ(yng)ԓMһˎҪӱáڑ(yng)fƽǰˎgm(dng)g(yng)M(jn)Rz飬ιܙz(Ҋ(jin)ע(xing))ˎgF(xin)(yn)ƤSȫYƤ(yng)ԓͣˎڌ(do)ʮ(ni)200mg/r(sh)F(xin)ƤtߵˎֱƤʧ(Ҋ(jin)ע(xing))߳F(xin)жȻضȸιܮ(GGT)(yng)ֹͣʹfƽֱιܻ֏(f)A(ch)ˮƽ֮fƽ(yng)200mg/_(ki)ʼoˎM(jn)һ^Ȼ֔(jn)ӄ200mg/ÿՃɴΡٴγF(xin)жȻضȸιܮfƽ(yng)ԓͣˎ(Ҋ(jin)ע(xing))ͣfƽ^(gu)(yng)սoˎԭt_(ki)ʼ200mgˎÿһΌ(do)룬֮ÿ200mgÿնΡ
ͨQ
fƽƬ
Σ
?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(jin)÷;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˚qăͯߣfƽĿڷ]ˎʼܰ4mg/kgһһνoˎ֮7mg/kgһɴνoˎ(du)ڰ˚qͰ˚qϵăͯ]ʼܰ4mg/kgһһ֮4mg/kgһɴκλÿˎó^(gu)400mg
3.A(y)HIVĸ(du)ڌRϷЋDfƽ]£
ĸH÷ڷ_(ki)ʼMܵؿڷ΄200mg
÷ڳ72Сr(sh)(ni)2mg/kg΄ڷˎa(chn)Dڮa(chn)냺ǰСr(sh)(ni)õfƽô(yng)2mg/kg΄ڷfƽһηˎ2472Сr(sh)(ni)2mg/kgٷһfƽ
(yng)֪߰̎ÿշfƽıҪ©ˎߑ(yng)ԓMһˎҪӱ
ڑ(yng)fƽǰˎgm(dng)g(yng)M(jn)Rz飬ιܙz(Ҋ(jin)ע(xing))
ˎgF(xin)(yn)ƤSȫYƤ(yng)ԓͣˎڌ(do)ʮ(ni)200mg/r(sh)F(xin)ƤtߵˎֱƤʧ(Ҋ(jin)ע(xing))
߳F(xin)жȻضȸιܮ(GGT)(yng)ֹͣʹfƽֱιܻ֏(f)A(ch)ˮƽ֮fƽ(yng)200mg/_(ki)ʼoˎM(jn)һ^죬Ȼ֔(jn)ӄ200mg/ÿՃɴΡٴγF(xin)жȻضȸιܮfƽ(yng)ԓͣˎ(Ҋ(jin)ע(xing))
ͣfƽ^(gu)(yng)սoˎԭt_(ki)ʼ200mgˎÿһΌ(do)֮ÿ200mgÿն
(yng)
ˣ
Ƥι⣬Rԇ(yn)cfƽίP(gun)Ҋ(jin)IJ(yng)Аƣl(f)ᡢ^ʹ˯IaʹͼʹdzٵĎؚѪѪpٰYcfƽίP(gun)fƽίĻP(gun)(ji)ʹĂ(g)(bo)
кr(yn)صˎﲻ(yng)Stevens-JohnsonCԱƤxذY/˥ߺ^(gu)(yng)ƤȫYl(f)ᡢP(gun)(ji)ʹʹܰͽY(ji)Լ(ni)KpסἚ(x)(x)ȱYIܓpʼ812ܵίǺP(gun)IAM(jn)Ҫ(yn)ܱO(jin)y(c)(Ҋ(jin)ע(xing))
ƤwƤ½M
fƽҊ(jin)RLJ(yn)Ƥ{Ƥw(yng)Stevens-JohnsonC(SJS)ͺҊ(jin)ĶԱƤx(TEN)fƽίĻߴs2%(hu)F(xin)Y
ɣ
1.(du)fƽĻԳɷߴˮa(chn)Ʒκx΄R@^(gu)(yng)Ļfƽ(yng)
2.(du)ڇ(yn)ƤƤȫY^(gu)(yng)fƽĸДfƽίĻ߲·
3.ڷfƽg^F(xin)ASATALAT>ֵ5(yng)fƽѸ?gu)?f)l(f)ιĻߑ(yng)(Ҋ(jin)ע(xing))
ע(xing)
Ʒί8ǺP(gun)IAΣ(du)rM(jn)Ї(yn)ܵıO(jin)y(c)r(sh)l(f)F(xin)ڵć(yn)غ{Ƥw(yng)(yn)صĸ/˥횇(yn)Ҫ14쌧(do)ڕr(sh)(du)ڱO(jin)y(c)lЌָÿһeӄ֮ǰӺ2
(du)KӰ푣
fƽίĻF(xin)(yn)صĸKԼđ֭ٷeԸΉ(yn)صĸKl(f)ίǰ12܃(ni)һЩ^tF(xin)
ͨڿί_(ki)ʼr(sh)ͳF(xin)ALTASTˮƽߣtίgKl(f)¼ΣU(xin)Ծ(yng)fƽίˡ
(yng)֪fƽҪĶnj(du)Kˎ8܃(ni)(yng)^ԓãO(jin)y(c)ALTASTˮƽˎgЪgҲ(yng)O(jin)y(c)ι
(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)ʴADZҪġڌ(do)ʮ(ni)F(xin)ƤtߵˎֱƤʧ
fƽίǰ14(ni)ͬr(sh)Ï(qing)(40mg/)ܽcfƽP(gun)Ƥڷfƽ6܃(ni)Ƥİl(f)
DŮfƽٲÿڷˎطM(jn)б
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)Mһˎo(w)횼ӱáfƽҪɸKxIM(jn)дx˸I˥ˎr(sh)Ҫeע⡣
(dng)fƽ鿹D(zhun)øwϵһ֕r(sh)_(ki)ʼˎǰ(yng)(du)ÿһɷ˽
ɷݣ
fƽ
Ԡ
ƷɫɫƬ
ˎã
fƽǸμ(x)ɫP450xø(CYP3ACYP2B)T(do)ҪCYP3ACYP2BxˎcfƽÕr(sh)fƽԽ@ЩˎѪ{(Ҋ(jin)ˎx(dng)W(xu))һ(g)ڽCYP3ACYP2Bxˎһ(g)(wn)ί_(ki)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(w)@13%;(du)BCmaxo(w)@ã5.8%B(zidovudine)(du)fƽˎ(dng)W(xu)o(w)Ӱһоfƽ(du)didonosine(n=18)zalcitabine(n=8)ķ(wn)B(ti)ˎ(dng)W(xu)o(w)Ӱ
(du)25HIVȾĻ(yng)fƽnelfinavir(70mgtid)stauvdine(30-40mgbid)ί36Rԇ(yn)Y(ji)@ʾstauvdineAUCCmaxo(w)y(tng)Ӌ(j)W(xu)@׃(du)90lamivudinefƽһMfƽӰοίĻM(jn)Ⱥˎ(dng)W(xu)оY(ji)@ʾlamivudine^ʺͷֲݷeo(w)׃@fƽ(du)lamivudineo(w)Ӱ푡
ǺD(zhun)øƄRԇ(yn)(14)Y(ji)@ʾfƽcefavirenzòӰfƽ(wn)B(ti)ˎ(dng)W(xu)(sh)efavirenzcfƽˎ@½efavirenzAUC½22%Cmax½36%cfƽҪCefavirenzÿӵ800mg
øƄԇ(yn)fƽˎ200mgÿһΣ֮200mgÿՃɴΣ28
Saqinavirһ(xing)Rԇ(yn)(31)УHIVȾĻ߷fƽsaqinavir(Ӳz600mgÿ)Y(ji)ߺÌ(do)saqinavirAUCƽ½24%(P=0.041)fƽѪ{ȟo(w)@׃(do)saqinavirӲzAUC½M(jn)һsaqinavirѪ{½õRxв(lin)ˎӰfƽˎ(dng)W(xu)
һ(xing)Rԇ(yn)(20)оÿһηsaqinavirܛzҺ100mgritonavirеĻ߶ͬr(sh)fƽоY(ji)cvʷ(du)ȣsaqinavirܛzҺ100mgritonaviròӰfƽˎ(dng)W(xu)(sh)saqinavirܛzҺ100mgritonavirÌ(du)fƽˎ(dng)W(xu)ӰRϛ](mi)@
Ritonavir(dng)fƽcritonavirÕr(sh){(dio)Rԇ(yn)(n=25)HIVȾͬr(sh)nevirapineritonavir(600mgÿՃɴÄuˎ)ίѪ{Ⱦo(w)@׃
IndinavirRԇ(yn)(n=25)HIVȾ߽fƽindinavir(800mg8Сr(sh)һ)ίindinavirAUCƽ½28%(P<0.01)fƽѪ{ȟo(w)@׃(du)fƽindinavirõĝӰ߀](mi)п϶RY(ji)ՓfƽcindinavirÕr(sh)(dng)fƽ200mgÿՃɴΕr(sh)indinavirɿ]ӵ1000mgÿСr(sh)һǣĿǰПo(w)Y@ʾoindinavir1000mgÿСr(sh)һfƽ200mgÿՃɴcindinavir800mgÿСr(sh)һΣfƽ200mgÿՃɴΣɷĶڻL(zhng)ڿкβͬ
Nelfinavirһ(xing)36Rԇ(yn)(n=25)(yng)fƽnelfinavir(75mgÿ)d4T(3040mgÿն)HIVȾߣںfƽnelfinavirˎ(dng)W(xu)(sh)](mi)нy(tng)Ӌ(j)W(xu)@׃(AUC+4%Cmax+14%Cmin-2%)cǰYȣfƽˎˮƽo(w)׃
(dng)fƽcκεøƄÕr(sh)Пo(w)ȫԽ͵Ĉ(bo)
ڽ־Ըкlopinavirfƽlopinavirˎ(dng)W(xu)(sh)](mi)аl(f)F(xin)@׃
ڽ(jng)^(gu)øƄΪ(d)ίĻУfƽlopinavirritonavir400/100mg(3(g)z)һɴԼD(zhun)øƄķ(yng)ʷdzá
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)УcǰYͪ(Ketoconazole)ʹfƽѪ{ˮƽ1528%ˣͪfƽ(yng)ϲˎfƽ(du)(itraconazole)ӰвmȻПo(w)ˎõԇ(yn)IKйĿˎ()ɴͪ
CYPͬøT(do)
ƽһ(g)_(ki)о(n=14)fƽ(du)ƽķ(wn)B(ti)ˎ(dng)W(xu)(sh)CmaxAUCo(w)@Ӱ෴ͬǰYƽ@fƽAUC(-58%)Cmax(-50%)Cmin(-68%)(dng)fƽƽÕr(sh)ĿǰПo(w)Yό(du)脩{(dio)M(jn)u(png)
fƽ200mgb.i.d.300mgq.d(ͬr(sh)ZDVøƄί150mgq.d)Y(ji)@ʾĝț](mi)@׃(AUCƽ12%Cminssƽ½3%)Cmaxss@(20%)Դxa(chn)25-O-desacety-lĝț](mi)@׃ͬӵоͬǰYʹfƽϵy(tng)@(9%)@Щ׃o(w)ҪRxͬr(sh)fƽǰȫҪ{(dio)
]ͬr(sh)fƽSt.JohnswortSt.JohnswortĮa(chn)Ʒ?yn)Ј?bo)@ʾSt.Johnswortˎ֮gSt.Johnswortͬr(sh)÷ǺշD(zhun)øƄfƽɽͷǺշD(zhun)øƄĝȣӰfƽˎЧʧȥʹa(chn)(du)fƽǺD(zhun)øƄˎ
CYPͬøƄfƽͿùصˎоY(ji)ˎÕr(sh)ùصAUC(-30%)Cmax(-21%)Cmin(-46%)@ùصĻԴx14-OHùصAUC(58%)Cmax(62%)@fƽCmin(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](mi)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(c)
Yϣ
˵ĸμ(x)wwоfƽuxa(chn)γɲܰ(dapsone)ƽS/ǰӰͪͼtùؿ@fƽuxa(chn)γПo(w)P(gun)Rԇ(yn)
(yng)ע(dng)cfƽÕr(sh)CYP3ACYP2B6ĵˎѪ{ȿ½ڌ(du)ɳͪxC(j)Ƶ˽fƽͨ^(gu)ӸδxܽɳͪѪ{ȡ(j)(bo)ͬr(sh)(yng)fƽɳͪίĻF(xin)CˣɳͪSֽoˎIJ˺fƽr(sh)hм(x)^C(du)ɳͪĄM(jn)(yng){(dio)
ˎã
ÙC(j)ƣ
fƽwȱݲHIV-1ķǺD(zhun)øƄNNRTIfƽcHIV-1D(zhun)øֱӽY(ji)ϣͨ^(gu)ƉԓøĴλc(din)(li)RNAهDNAهDNAۺøĻfƽcծa(chn)(jng)(zhng)fƽ(du)HIV-2D(zhun)ø˼(x)DNAۺø(DNAۺøû)o(w)
wԣwHIV-1(du)fƽcw(ni)fƽHIV-1(f)P(gun)δ_fƽw⿹ͨ^(gu)Ѫκ˼(x)ɼ(x)ܰͼ(x)(li)y(c)ģ䌦(du)(sh)(yn)ҼRxHIV-1IC50딵(sh)Ɲȣ10-100nM(x)B(yng)ԇ(yn)ʾfƽcRȥuա˾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)HIVꡣP(gun)ڷǺD(zhun)øƄfƽcD(zhun)øƄĽˎԔ(sh)(j)߀4(g)wy(c)Rˎxꌦ(du)fƽԣ6(g)wy(c)fƽˎxꌦ(du)RȥuվøIJͬfƽcHIVøƄF(xin)ˎԵĿԲ
ϺF(xin)ɭ h(hun)ô,ϺF(xin)ɭ h(hun)ôʹt(y)ˎW(wng)ˎƷ(k)lṩϺF(xin)ɭ h(hun)f(shu)(sh),ϺF(xin)ɭ h(hun)r(ji),ϺF(xin)ɭ h(hun)X(qin),ϺF(xin)ɭ h(hun)...
ϺF(xin)ɭ ̩ô,ϺF(xin)ɭ ̩ôʹt(y)ˎW(wng)ˎƷ(k)lṩϺF(xin)ɭ ̩f(shu)(sh),ϺF(xin)ɭ ̩Ƀr(ji),ϺF(xin)ɭ ̩ɶX(qin),ϺF(xin)ɭ ̩ɵĹЧc...
ϺF(xin)ɭ ̹ô,ϺF(xin)ɭ ̹ôʹt(y)ˎW(wng)ˎƷ(k)lṩϺF(xin)ɭ ̹f(shu)(sh),ϺF(xin)ɭ ̹r(ji),ϺF(xin)ɭ ̹X(qin),ϺF(xin)ɭ ...
ϺF(xin)ɭ uAô,ϺF(xin)ɭ uAôʹãt(y)ˎW(wng)ˎƷ(k)lṩϺF(xin)ɭ uAf(shu)(sh),ϺF(xin)ɭ uAr(ji),ϺF(xin)ɭ uAX(qin),ϺF(xin)...
ϺF(xin) L(fng)ɰلô,ϺF(xin) L(fng)ɰلôʹt(y)ˎW(wng)ˎƷ(k)lṩϺF(xin) L(fng)ɰلf(shu)(sh),ϺF(xin) L(fng)ɰلr(ji),ϺF(xin) L(fng)ɰلX(qin),ϺF(xin) L(fng)ɰلĹЧc...
ˎI(y) עҺô,ˎI(y) עҺôʹãt(y)ˎW(wng)ˎƷ(k)lṩˎI(y) עҺf(shu)(sh),ˎI(y) עҺr(ji),ˎI(y) עҺX(qin),ˎI(y) ע...
Fݿƕ zô,Fݿƕ zôʹt(y)ˎW(wng)ˎƷ(k)lṩFݿƕ zf(shu)(sh),Fݿƕ z҃r(ji),Fݿƕ zҶX(qin),Fݿƕ z...