锟斤拷一锟斤拷锟斤拷锟絬(p锟斤拷ng)锟絩(ji锟斤拷)锟侥大背撅拷锟斤拷锟斤拷锟斤拷(gu锟斤拷)锟揭局革拷锟斤拷(j锟斤拷)锟斤拷锟斤拷(gu锟斤拷)锟斤拷(w锟斤拷)院锟絇(gu锟斤拷n)锟节改革拷藥品锟絫(y锟斤拷)锟斤拷锟斤拷械锟斤拷锟絬(p锟斤拷ng)锟斤拷锟斤拷锟狡度碉拷锟斤拷見锟斤拷锟斤拷锟斤拷(gu锟斤拷)锟絣(f锟斤拷)锟斤拷2015锟斤拷44號(h锟斤拷o)锟斤拷锟皆硷拷锟斤拷锟斤拷(gu锟斤拷)锟斤拷(w锟斤拷)院锟絢锟斤拷锟絛锟絇(gu锟斤拷n)锟斤拷锟絖展锟斤拷锟斤拷藥锟絴(zh锟斤拷)锟斤拷锟酵拷效一锟斤拷锟斤拷锟絬(p锟斤拷ng)锟絩(ji锟斤拷)锟斤拷锟斤拷見锟斤拷锟斤拷锟斤拷(gu锟斤拷)锟絢锟絣(f锟斤拷)锟斤拷2016锟斤拷8號(h锟斤拷o)锟斤拷锟斤拷锟皆硷拷順戯拷(y锟斤拷ng)藥锟斤拷锟叫撅拷锟絖锟絣(f锟斤拷)锟侥現(xi锟斤拷n)锟斤拷(sh锟斤拷)锟斤拷锟絣(f锟斤拷)锟斤拷锟斤拷锟斤拷锟斤拷FDA.Guidance for industry: “Waiver of in invo bioequivalence studies forimmediate-release solid oral dosage forms based on a BiopharmaceuticsClassification System”锟斤拷指锟斤拷锟斤拷锟狡讹拷锟斤拷锟揭囷拷(gu锟斤拷)锟斤拷锟斤拷锟絯锟斤拷锟斤拷锟叫э拷锟皆囷拷(y锟斤拷n)锟斤拷锟斤拷指锟斤拷(d锟斤拷o)原锟絫锟斤拷該指锟斤拷(d锟斤拷o)原锟絫锟角伙拷锟节囷拷(gu锟斤拷)锟紿锟斤拷锟絁(r锟斤拷n)锟斤拷锟斤拷锟斤拷藥锟斤拷锟絎(xu锟斤拷)锟斤拷锟较碉拷y(t锟斤拷ng)锟斤拷BiopharmaceuticsClassification System锟斤拷锟斤拷锟铰猴拷(ji锟斤拷n)锟絈BCS锟斤拷锟斤拷锟�锟斤拷锟斤拷锟斤拷锟节凤拷锟斤拷藥锟絴(zh锟斤拷)锟斤拷锟酵拷效一锟斤拷锟斤拷锟絬(p锟斤拷ng)锟絩(ji锟斤拷)锟叫口凤拷锟斤拷锟絯锟斤拷锟斤拷苿锟斤拷锟秸�(q锟斤拷ng)锟斤拷锟斤拷锟叫э拷裕锟紹ioequivalence锟斤拷锟斤拷锟斤拷锟斤拷BCS系锟統(t锟斤拷ng)锟角帮拷锟斤拷藥锟斤拷锟剿拷锟斤拷院锟斤拷c锟斤拷锟紹透锟皆岋拷(du锟斤拷)锟斤拷锟組(j锟斤拷n)锟叫凤拷類碉拷一锟斤拷(g锟斤拷)锟狡學(xu锟斤拷)锟杰橈拷(g锟斤拷u)锟斤拷锟斤拷(d锟斤拷ng)锟芥及锟斤拷锟节凤拷锟斤拷锟絯锟斤拷锟斤拷苿锟斤拷谢锟斤拷锟剿庯拷锟缴分ｏ拷Active Pharmaceutical Ingredient锟斤拷锟斤拷锟铰猴拷(ji锟斤拷n)锟絈API锟斤拷锟斤拷锟絯锟斤拷(n锟斤拷i)锟斤拷锟斤拷锟劫度和程度時(sh锟斤拷)锟斤拷BCS系锟統(t锟斤拷ng)锟斤拷要锟斤拷锟絔锟斤拷锟斤拷锟斤拷锟斤拷(g锟斤拷)锟絇(gu锟斤拷n)锟絀锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷藥锟斤拷锟杰斤拷锟皆ｏ拷Solubility锟斤拷锟斤拷锟絚锟斤拷锟紹透锟皆ｏ拷Intestinal permeability锟斤拷锟斤拷锟狡勶拷锟杰筹拷锟饺ｏ拷Dissolution锟斤拷锟斤拷

 

 

锟斤拷锟斤拷(j锟斤拷)BCS锟斤拷锟较碉拷y(t锟斤拷ng)锟斤拷藥品锟斤拷锟街烇拷锟斤拷锟斤拷锟斤拷類ｏ拷

 

锟斤拷一類ｏ拷锟斤拷锟杰斤拷锟斤拷锟斤拷锟竭滲透锟皆ｏ拷High Solubility- HighPermeability锟斤拷

锟节讹拷類ｏ拷锟斤拷锟杰斤拷锟斤拷锟斤拷锟竭滲透锟皆ｏ拷Low Solubility-HighPermeability锟斤拷

锟斤拷锟斤拷類ｏ拷锟斤拷锟杰斤拷锟皆★拷锟酵滲透锟皆ｏ拷High Solubility-LowPermeability锟斤拷

锟斤拷锟斤拷類ｏ拷锟斤拷锟杰斤拷锟斤拷锟斤拷锟酵滲透锟皆ｏ拷Low Solubility-LowPermeability锟斤拷

 

指锟斤拷指锟斤拷锟斤拷锟斤拷(d锟斤拷ng)锟节凤拷锟斤拷锟絯锟斤拷锟斤拷苿锟斤拷锟斤拷w锟斤拷(n锟斤拷i)锟斤拷锟杰筹拷锟斤拷锟斤拷(du锟斤拷)锟斤拷胃锟脚空時(sh锟斤拷)锟絞锟斤拷锟角�锟斤拷锟�锟斤拷锟斤拷锟揭撅拷锟叫很高碉拷锟杰斤拷葧r(sh锟斤拷)锟斤拷藥锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷屎锟斤拷锟斤拷粘潭染筒锟斤拷锟�(hu锟斤拷)锟斤拷賴锟斤拷藥锟斤拷锟斤拷艹锟斤拷r(sh锟斤拷)锟絞锟斤拷锟斤拷胃锟絚锟斤拷锟斤拷通锟絕锟絩(sh锟斤拷)锟絞锟斤拷锟斤拷耍锟斤拷锟斤拷@锟絅锟斤拷r锟斤拷锟斤拷锟斤拷(du锟斤拷)锟斤拷BCS锟斤拷锟�1類猴拷3類碉拷藥锟斤，只要處锟斤拷锟叫碉拷锟斤拷锟斤拷锟給锟较成分诧拷锟紷锟斤拷影锟紸PI锟斤拷锟斤拷锟斤拷锟斤拷锟絫锟斤拷锟斤拷锟紺锟斤拷該藥锟斤拷锟斤拷锟絯锟斤拷(n锟斤拷i)锟斤拷锟斤拷锟斤拷锟矫度猴拷锟斤拷锟斤拷锟叫э拷目锟斤拷锟斤拷锟�锟斤拷锟斤拷锟斤拷锟斤拷锟叫э拷曰锟斤拷狻�

 

锟斤拷一锟斤拷锟斤拷(du锟斤拷)锟斤拷BCS1類碉拷藥锟斤拷锟斤拷要锟紺锟斤拷锟斤拷锟铰庯拷锟絚(di锟斤拷n)锟斤拷

 

1锟斤拷藥锟斤拷锟斤拷懈锟斤拷芙锟斤拷锟�锟斤拷

2锟斤拷藥锟斤拷锟斤拷懈邼B透锟皆ｏ拷

3锟斤拷锟斤拷锟狡和咃拷锟斤拷锟狡勶拷锟斤拷锟斤拷锟斤拷锟斤拷艹锟斤拷锟�30min>85%锟斤拷锟斤拷锟斤拷锟斤拷锟狡勶拷锟叫诧拷锟斤拷锟斤拷影锟斤拷锟剿庯拷煞锟斤拷锟斤拷锟斤拷锟斤拷屎锟斤拷锟斤拷粘潭鹊锟斤拷魏锟斤拷o锟斤拷锟斤拷

 

锟斤拷锟斤拷锟斤拷锟斤拷(du锟斤拷)锟斤拷BCS3類碉拷藥锟斤拷锟斤拷要锟紺锟斤拷锟斤拷锟铰庯拷锟絚(di锟斤拷n)锟斤拷

 

1锟斤拷藥锟斤拷锟斤拷懈锟斤拷芙锟斤拷裕锟�

2锟斤拷锟斤拷锟狡和咃拷锟斤拷锟狡勶拷锟斤拷锟斤拷锟叫非�锟斤拷锟斤拷俚锟斤拷艹锟�(15min>85%锟斤拷)锟斤拷

3锟斤拷锟斤拷锟斤拷锟狡勶拷锟酵咃拷锟斤拷锟狡勶拷锟斤拷(y锟斤拷ng)處锟斤拷锟斤拷全锟斤拷同锟斤拷锟斤拷锟組锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷

 

藥锟斤拷锟杰斤拷锟皆的測(c锟斤拷)锟斤拷锟斤拷(sh锟斤拷)锟斤拷(j锟斤拷)锟斤拷锟斤拷(du锟斤拷)锟斤拷(ji锟斤拷n)锟斤拷锟阶碉拷锟斤拷锟揭撅拷锟斤拷锟斤拷锟矫碉拷锟截現(xi锟斤拷n)锟皆★拷原锟絫锟叫岋拷(du锟斤拷)锟斤拷锟杰斤拷锟皆讹拷锟絰锟介：?ji锟斤拷n)未谓o藥锟斤拷锟斤拷邉锟斤拷锟斤拷锟�(du锟斤拷)锟斤拷(y锟斤拷ng)锟斤拷API锟斤拷锟絯锟絜锟斤拷250ml锟斤拷锟斤拷锟斤拷伲锟�锟斤拷pH值锟斤拷1.0—6.8锟斤拷锟斤拷锟斤拷(n锟斤拷i)锟斤拷水锟斤拷锟皆斤拷锟絴(zh锟斤拷)锟斤拷锟斤拷锟斤拷全锟杰斤拷锟斤拷锟斤拷倩锟角�锟斤拷锟斤拷锟斤拷艹锟揭诧拷锟斤拷圆锟斤拷锟斤拷艹锟斤拷x锟組(j锟斤拷n)锟叫測(c锟斤拷)锟斤拷锟紷锟斤拷锟斤拷

 

然锟斤拷锟斤拷锟斤拷要BE锟斤拷锟斤拷BCS1锟斤拷3锟剿庯拷锟�锟斤拷锟斤拷锟节兩达拷锟斤拷K锟斤拷

 

锟斤拷1锟斤拷藥锟斤拷B透锟皆ｏ拷锟斤拷2锟斤拷锟給锟较诧拷影锟剿庯拷锟斤拷锟斤拷锟斤拷俣群锟斤拷锟斤拷粘潭锟�锟斤拷锟紷锟斤拷锟竭撅拷锟斤拷锟斤拷锟紺锟斤拷锟斤拷锟斤拷H锟紿通锟絕锟侥獻(xi锟斤拷n)锟斤拷(b锟斤拷o)锟斤拷锟斤拷锟叫撅拷锟斤拷锟絝锟斤拷锟斤拷锟絬(p锟斤拷ng)锟紺(j锟斤拷)锟斤拷(g锟斤拷u)锟角硷拷锟斤拷锟斤拷锟統锟斤拷锟斤拷锟紷也锟杰忥拷FDA锟斤拷PMDA锟饺監(ji锟斤拷n)锟杰機(j锟斤拷)锟斤拷(g锟斤拷u)锟斤拷(du锟斤拷)BE锟斤拷锟斤拷锟斤拷锟街碉拷謹(j锟斤拷n)锟斤拷锟紹(t锟斤拷i)锟斤拷锟较匡拷見一锟斤拷锟斤拷锟斤拷(du锟斤拷)锟节匡拷锟斤拷影锟剿庯拷锟斤拷锟斤拷锟斤拷D(zhu锟斤拷n)锟絓(y锟斤拷n)锟斤拷锟給锟较帮拷锟斤拷锟斤拷锟斤拷锟斤拷詣锟�锟斤拷锟紹透锟斤拷锟絳(di锟斤拷o)锟斤拷(ji锟斤拷)锟斤拷锟斤拷锟斤拷露锟斤拷锟斤拷山锟芥醇锟饺ｏ拷锟斤拷锟皆硷拷脂锟絴(zh锟斤拷)锟斤拷硬脂锟斤拷锟斤拷锟斤拷锟�锟斤拷锟斤拷锟斤拷龋锟斤拷锟斤拷鐓拷锟斤拷苿锟教庯拷锟斤拷锟斤拷锟斤拷舜锟斤拷锟斤拷锟絴(zh锟斤拷)锟斤拷锟絆(ji锟斤拷n)锟杰機(j锟斤拷)锟斤拷(g锟斤拷u)锟斤拷(du锟斤拷)锟斤拷BE锟斤拷锟斤拷锟斤拷锟斤拷锟劫戯拷(y锟斤拷ng)锟斤拷(hu锟斤拷)要锟斤拷锟斤拷锟剿庯拷锟絀(y锟斤拷)锟紺锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷全一锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷還要锟斤拷锟叫撅拷锟斤拷锟斤拷锟斤拷詣锟斤拷锟斤拷锟斤拷锟斤拷植锟斤拷锟斤拷弑锟斤拷锟斤拷锟皆勶拷锟杰筹拷锟斤拷锟绞ｏ拷锟斤拷锟斤拷锟斤拷锟紺锟斤拷锟斤拷

 

锟斤拷(du锟斤拷)锟节滲透锟斤拷锟斤拷目前FDA锟斤拷EMA锟饺岋拷锟絬(p锟斤拷ng)锟紺锟斤拷锟叫讹拷锟斤拷(hu锟斤拷)锟斤拷露原锟斤拷锟斤拷I(y锟斤拷)锟斤拷锟斤拷锟斤拷藥锟斤拷BCS锟斤拷锟斤拷芯锟斤拷Y(ji锟斤拷)锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷懦潭锟斤拷锟揭拷锟斤拷锟剿庯拷锟絀(y锟斤拷)锟組(j锟斤拷n)锟斤拷锟斤拷锟斤拷锟斤拷锟�(x锟斤拷)锟铰地凤拷锟斤拷锟絚锟剿岋拷(sh锟斤拷)锟斤拷锟斤拷锟斤拷锟斤拷M(j锟斤拷n)“锟斤拷”锟叫讹拷锟斤拷锟斤拷知锟斤拷锟斤拷锟絖(d锟斤拷)沙锟斤拷锟斤拷锟斤拷锟�锟斤拷锟斤拷FDA锟斤拷锟絖锟侥綜锟斤拷锟侥硷拷Sprycel_ClinPharmR锟斤拷锟斤拷锟揭傦拷锟斤拷锟斤拷锟揭碉拷锟斤拷BCS锟斤拷2锟�锟斤拷锟斤拷锟斤拷锟杰斤拷雀邼B透锟斤拷锟斤拷原锟侥匡拷锟节綜锟斤拷锟叫碉拷39锟斤拷业锟�锟斤拷锟斤拷锟铰ｏ拷

 

                           

锟杰斤拷葦锟�(sh锟斤拷)锟斤拷(j锟斤拷)也锟斤拷同一頁冿拷(n锟斤拷i)锟斤拷锟杰斤拷葹锟絧H锟斤拷賴锟斤拷锟斤拷pH7.0锟絩(sh锟斤拷)<1μg/ml锟斤拷pH6锟絩(sh锟斤拷)~8μg/ml锟斤拷锟斤拷锟铰ｏ拷

 

 

 

锟紹透锟斤拷锟叫撅拷锟結(ji锟斤拷)論锟斤拷锟铰ｏ拷

 

 

锟結锟斤拷锟紷示锟斤拷锟斤拷锟斤拷caco-2锟斤拷(x锟斤拷)锟斤拷锟斤拷(sh锟斤拷)锟�(y锟斤拷n)?z锟斤拷i)锟斤拷停?/span>一锟絅锟剿匡拷隆锟結(ji锟斤拷)锟絚锟劫帮拷锟斤拷(x锟斤拷)锟斤拷锟斤拷锟結(ji锟斤拷)锟斤拷(g锟斤拷u)锟酵癸拷锟斤拷锟斤拷锟斤拷诜只锟斤拷锟叫★拷c锟斤拷皮锟斤拷(x锟斤拷)锟斤拷锟斤拷锟斤拷锟斤拷微锟絨毛锟饺結(ji锟斤拷)锟斤拷(g锟斤拷u)锟斤拷锟斤拷锟斤拷锟斤拷锟絚小锟絚刷锟筋緣锟斤拷皮锟斤拷锟絇(gu锟斤拷n)锟斤拷酶系锟斤拷锟斤拷锟矫侊拷模锟組锟絯锟斤拷(n锟斤拷i)锟絚锟紻(zhu锟斤拷n)锟絓(y锟斤拷n)锟侥岋拷(sh锟斤拷)锟�(y锟斤拷n)锟斤拷锟斤拷通锟絕锟絚FDA锟斤拷锟絔锟侥高滲透锟皆冿拷(n锟斤拷i)锟斤拷(bi锟斤拷o)藥锟斤拷锟斤拷锟斤拷锟藉爾锟酵碉拷锟斤拷锟斤拷锟缴憋拷锟絕锟斤拷锟絖锟斤拷锟絖(d锟斤拷)沙锟斤拷锟斤拷锟竭滲透锟斤拷藥锟斤拷锟斤拷锟斤拷痛锟斤拷J(r锟斤拷n)锟斤拷锟戒定锟絰锟斤拷邼B透锟斤拷锟角猴拷锟斤拷锟斤拷锟斤拷锟斤拷锟揭傦拷锟酵曪拷(hu锟斤拷)锟斤拷锟斤拷 “锟斤拷锟斤拷”锟斤拷

 

锟斤拷锟饺ｏ拷F(xi锟斤拷n)DA锟斤拷锟絬(p锟斤拷ng)锟絋锟斤拷锟较圖锟斤拷指锟斤拷锟紹透锟皆結(ji锟斤拷)锟斤拷锟斤拷(y锟斤拷ng)refer to section 2.2.5.5 for in vivo permeability锟斤拷锟揭傦拷锟揭碉拷p26锟叫此诧拷锟街冿拷(n锟斤拷i)锟捷ｏ拷锟斤拷旨锟斤拷锟叫撅拷锟絖(d锟斤拷)沙锟斤拷锟斤拷锟斤拷锟斤拷要通锟絕锟絀锟終锟斤拷锟斤拷K锟斤拷锟絰锟斤拷锟斤拷锟斤拷途锟斤拷锟斤拷通锟絕锟統(c锟斤拷)锟斤拷锟斤拷锟斤拷锟皆橈拷(bi锟斤拷o)記藥锟斤，锟斤拷锟斤拷锟絖(d锟斤拷)沙锟斤拷锟斤拷锟絀锟終锟斤拷锟斤拷锟斤拷锟角筹拷锟斤拷锟斤拷锟斤拷锟斤拷锟絕85%锟斤拷通锟絕锟絊锟斤拷锟斤拷锟斤拷锟斤拷锟絊锟斤拷锟斤拷原锟斤拷藥锟斤拷锟斤拷锟斤拷19.1%锟斤拷锟結(ji锟斤拷)锟斤拷锟斤拷锟铰圖锟斤拷

 

 

同锟絩(sh锟斤拷)锟給藥锟斤拷2h血锟絳锟斤拷锟絖(d锟斤拷)沙锟斤拷锟斤拷M21锟斤拷锟絰锟斤（sulfate conjugate锟斤拷锟斤拷锟斤拷锟�(f锟斤拷)锟斤拷锟斤）水平锟絖(d锟斤拷)锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷缘锟�9.5%锟斤拷锟斤拷锟斤拷锟絖(d锟斤拷)沙锟斤拷锟斤拷锟斤拷軙锟�(hu锟斤拷)锟斤拷胃锟絚锟斤拷锟斤拷(j锟斤拷ng)锟斤拷锟斤拷脂酶锟斤拷锟絰锟斤拷

 

 

锟紺锟较凤拷锟斤拷锟斤拷锟絖(d锟斤拷)沙锟斤拷锟斤拷原锟斤拷藥19.1%通锟絕锟絊锟斤拷锟斤拷泄锟斤拷锟斤拷锟斤拷锟斤拷锟絯锟斤拷(n锟斤拷i)锟絕锟斤拷(du锟斤拷)锟斤拷锟斤拷锟斤拷锟矫度戯拷(y锟斤拷ng)小锟斤拷85%锟斤拷锟斤拷藥锟斤拷锟斤拷胃锟絚锟斤拷锟斤拷锟节憋拷锟斤拷锟絰锟斤拷锟斤拷锟斤拷

 

FDA 2015锟斤拷BE锟斤拷锟斤拷指锟斤拷[1]锟叫岋拷(du锟斤拷)锟节高滲透锟皆的讹拷锟絰锟介：

 

A drug substance is considered to be highly permeable when the extentof  absorption in humans is determined tobe 85 percent or more of an administered dose based on a mass balancedetermination (along with evidence showing stability of the drug in the GItract) or in comparison to an intravenous reference dose.锟斤拷锟斤拷锟斤拷(du锟斤拷)锟絚锟斤拷锟給藥锟斤拷锟斤拷锟斤拷锟节凤拷锟斤拷锟秸程讹拷≥85%锟斤拷锟斤拷锟斤拷锟絴(zh锟斤拷)锟斤拷平锟斤拷锟叫撅拷-同锟絩(sh锟斤拷)锟紺锟斤拷藥锟斤拷锟斤拷胃锟絚锟斤拷锟侥凤拷(w锟斤拷n)锟斤拷锟斤拷锟斤拷锟斤拷锟絚锟給锟絵注锟斤拷锟斤拷龋锟�锟斤拷

 

锟竭滲透锟皆測(c锟斤拷)锟斤拷锟斤拷锟斤拷(j锟斤拷)锟斤拷

 

Thepermeability class of a drug substance can be determined in human subjects using mass balance, orabsolute BA, which are the preferred methods, or intestinal perfusionapproaches. In many cases, a single method may be sufficient: (i) when theabsolute BA is 85 percent or more, or (ii) when 85 percent or more of theadministered drug is excreted unchanged in urine, or (iii) when 85 percent ormore of the administered drug is recovered in urine as parent and metaboliteswith evidence indicating stability in the GI tract. 锟紹透锟皆匡拷通锟絕锟斤拷锟絯锟斤拷試锟竭碉拷锟絴(zh锟斤拷)锟斤拷平锟斤拷锟絕锟斤拷(du锟斤拷)锟斤拷锟斤拷锟斤拷锟矫度ｏ拷锟斤拷(y锟斤拷u)锟斤拷锟絰锟今）伙拷锟絚锟斤拷锟斤拷注锟叫撅拷锟絖锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷一锟斤拷锟斤拷锟斤拷锟缴ｏ拷1锟斤拷锟絕锟斤拷(du锟斤拷)锟斤拷锟斤拷锟斤拷锟矫讹拷≥85%锟斤拷2锟斤拷锟斤拷≥85%藥锟斤拷锟斤拷原锟斤拷通锟絕锟斤拷锟斤拷泄锟斤拷3锟斤拷锟斤拷≥85%藥锟斤拷锟斤拷原锟酵和达拷锟絰锟斤拷锟斤拷式锟斤拷锟斤拷液锟斤拷锟斤拷-同锟絩(sh锟斤拷)锟紺锟斤拷藥锟斤拷锟斤拷胃锟絚锟斤拷锟侥凤拷(w锟斤拷n)锟斤拷锟皆ｏ拷胃锟絚锟斤拷锟斤拷(w锟斤拷n)锟斤拷锟斤拷前锟斤拷锟斤拷锟斤拷液锟叫达拷锟絰锟斤拷锟较碉拷y(t锟斤拷ng)锟斤拷锟絰锟斤拷锟斤拷胃锟絚锟斤拷锟斤拷锟絰锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷泄锟斤拷锟斤拷锟斤拷藥锟斤拷锟斤拷USP锟斤拷锟絔锟斤拷模锟組胃液1h锟斤拷模锟組锟絚液锟斤拷3h锟侥斤拷锟斤拷>5%锟斤拷锟絁(r锟斤拷n)锟介不锟斤拷(w锟斤拷n)锟斤拷锟斤拷

 

锟斤拷锟�锟斤拷锟斤拷锟斤拷锟絁(r锟斤拷n)锟斤拷原锟叫岋拷(du锟斤拷)锟絖(d锟斤拷)沙锟斤拷锟斤拷锟絯锟斤拷(n锟斤拷i)锟絴(zh锟斤拷)锟斤拷平锟斤拷锟叫撅拷锟結(ji锟斤拷)锟斤拷锟斤拷支锟街高滲透锟斤拷锟叫旓拷锟斤拷锟斤拷(j锟斤拷)锟斤拷85%锟斤拷锟较碉拷原锟斤拷藥锟斤拷锟斤拷锟揭猴拷锟斤拷懦锟斤拷锟轿革拷c锟斤拷锟斤拷(w锟斤拷n)锟斤拷锟斤拷锟斤拷锟絔锟叫絕锟斤拷(du锟斤拷)锟斤拷锟斤拷锟斤拷锟矫讹拷>85%锟斤拷(sh锟斤拷)锟斤拷(j锟斤拷)锟斤拷锟绞咃拷锟斤拷原锟叫岋拷锟絬(p锟斤拷ng)锟紺锟斤拷锟結锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷BCS锟斤拷類結(ji锟斤拷)論锟斤拷锟酵很匡拷锟杰曪拷(hu锟斤拷)锟絗锟斤拷(d锟斤拷o)锟斤拷锟斤拷藥锟叫撅拷锟剿員锟斤拷

 

锟斤拷锟�锟斤拷锟揭傦拷?n锟斤拷i)锟斤拷锟斤拷M(j锟斤拷n)一锟斤拷锟叫硷拷(x锟斤拷)锟斤拷x锟斤拷還锟斤拷锟斤拷p35頁發(f锟斤拷)锟紽(xi锟斤拷n)藥锟斤拷锟斤拷锟斤拷诺锟斤拷祝锟絧-gp锟斤拷锟斤拷锟斤拷锟叫撅拷锟斤拷锟斤拷锟铰圖锟斤拷

 

 

锟叫撅拷锟絣(f锟斤拷)锟紽(xi锟斤拷n)锟斤拷Caco-2試锟�(y锟斤拷n)锟斤拷藥锟斤拷锟饺烇拷50μM锟絩(sh锟斤拷)锟斤拷锟紹透系锟斤拷(sh锟斤拷)A-B锟剿烇拷102nm/s锟斤拷B-A锟剿烇拷222nm/s锟斤拷锟斤拷锟斤拷锟絖(d锟斤拷)沙锟斤拷锟斤拷锟絧-gp锟斤拷锟斤拷锟斤拷锟紷锟斤拷锟叫撅拷锟結(ji锟斤拷)锟斤拷锟叫匡拷锟皆匡拷锟斤拷FDA锟斤拷(du锟斤拷)锟斤拷锟叫撅拷锟斤拷锟揭拷螅簯锟�(y锟斤拷ng)锟斤拷锟斤拷一系锟斤拷藥锟斤拷锟饺讹拷锟斤拷锟紿锟紿锟角嗭拷一锟斤拷50μM锟斤拷锟皆硷拷使锟斤拷锟窖斤拷(j锟斤拷ng)p-gp锟斤拷锟斤拷锟組(j锟斤拷n)锟斤拷锟斤拷詫锟�(du锟斤拷)锟斤拷锟斤拷锟揭傦拷锟斤拷(y锟斤拷ng)該锟斤拷锟斤拷锟斤拷锟絖(d锟斤拷)沙锟斤拷锟斤拷锟斤拷锟斤拷锟�488锟斤拷50μM 锟斤拷葥Q锟斤拷锟�24.4μg/ml锟斤拷該锟斤拷锟斤拷呀锟�(j锟斤拷ng)锟絟(yu锟斤拷n)锟絟(yu锟斤拷n)锟斤拷锟絕藥锟斤拷锟斤拷pH7锟斤拷锟絴(zh锟斤拷)锟叫碉拷飽猴拷锟杰斤拷龋锟�<1μg/ml锟斤拷锟斤拷锟斤拷味锟斤拷锟斤拷B透锟皆結(ji锟斤拷)锟斤拷锟斤拷p-gp锟結(ji锟斤拷)锟斤拷锟斤拷锟斤拷锟杰凤拷锟斤拷(y锟斤拷ng)锟絯锟斤拷(n锟斤拷i)锟芥實(sh锟斤拷)锟斤拷r锟斤拷锟紷锟斤拷锟斤拷?y锟斤拷n)锟斤拷诓锟斤拷锟絚aco-2锟斤拷(x锟斤拷)锟斤拷模锟斤拷锟叫撅拷锟紹透锟皆時(sh锟斤拷)锟斤拷藥锟斤拷通锟斤拷使锟斤拷DMSO锟杰斤拷锟斤拷筛邼锟斤拷锟斤拷液锟斤拷锟斤拷稀釋碉拷锟斤拷(x锟斤拷)锟斤拷锟斤拷锟紹(y锟斤拷ng)锟斤拷锟斤拷锟斤拷锟斤拷锟杰獲锟斤拷50μM锟侥濓拷锟�锟斤拷锟斤拷锟斤拷锟絯锟斤拷(n锟斤拷i)锟斤拷?y锟斤拷n)锟剿庯拷锟斤拷芙锟饺低ｏ拷锟阶猴拷锟斤拷锟斤拷锟斤拷锟絖(d锟斤拷)锟斤拷該锟斤拷锟�锟斤拷锟斤拷Y(ji锟斤拷)锟斤拷锟酵曪拷(hu锟斤拷)偏锟絰锟斤拷(sh锟斤拷)锟紿锟斤拷锟絘(ch锟斤拷n)锟斤拷锟絗锟斤拷(d锟斤拷o)锟侥結(ji锟斤拷)論锟斤拷藥锟斤拷锟芥實(sh锟斤拷)锟紹透锟斤拷锟斤拷要锟斤拷锟絔藥锟斤拷锟紸-B锟剿的滲透系锟斤拷(sh锟斤拷)锟絚p-gp锟斤拷锟斤拷锟脚碉拷锟阶岋拷(du锟斤拷)藥锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷锟�锟斤拷锟斤拷锟斤拷邼锟饺碉拷藥锟斤拷锟斤拷詫锟�(d锟斤拷o)锟斤拷p-gp飽和ｏ拷锟絫锟斤拷(hu锟斤拷)锟斤拷锟斤拷锟紹透锟斤拷锟斤拷锟斤拷未飽猴拷p-gp锟絩(sh锟斤拷)锟侥滲透锟皆曪拷(hu锟斤拷)锟斤拷锟斤拷锟斤拷锟斤拷(du锟斤拷)锟絖(d锟斤拷)沙锟斤拷锟斤拷锟斤拷锟�锟斤拷锟斤拷锟絧-gp锟斤拷锟斤拷锟斤拷锟斤拷锟絚锟斤拷飽猴拷锟杰斤拷锟斤拷锟斤拷@锟斤拷锟斤拷50μM锟斤拷锟斤拷锟統(c锟斤拷)锟斤拷锟矫碉拷锟斤拷A-B锟剿滲透系锟斤拷(sh锟斤拷)锟酵匡拷锟斤拷锟斤拷偏锟竭碉拷锟斤拷锟紷也锟斤拷FDA要锟斤拷锟叫撅拷锟斤拷同藥锟斤拷锟斤拷锟铰的滲透系锟斤拷(sh锟斤拷)之原锟斤拷

 

藥锟斤拷锟斤拷要锟斤拷小锟絚锟斤拷锟斤拷锟斤拷小锟絚锟斤拷同锟絕(q锟斤拷)锟斤拷锟絧H值锟斤拷同锟斤拷锟斤拷偏锟斤拷锟皆碉拷锟斤拷锟斤拷直锟斤拷锟斤拷锟紸锟斤拷锟斤拷也锟斤拷(hu锟斤拷)影響碉拷锟斤拷A藥锟斤拷慕锟斤拷x锟教度從讹拷影锟剿庯拷锟斤拷锟斤拷锟�锟斤拷锟斤拷锟�锟斤拷caco-2锟斤拷(x锟斤拷)锟斤拷試锟�(y锟斤拷n)锟斤拷A锟剿ｏ拷锟斤拷(x锟斤拷)锟斤拷锟侥わ拷锟斤拷锟絧H也锟斤拷(y锟斤拷ng)锟斤拷锟絔锟节冿拷(n锟斤拷i)锟斤拷锟叫撅拷锟絣(f锟斤拷)锟紽(xi锟斤拷n)锟斤拷锟斤拷锟斤拷锟�锟斤拷酮锟斤拷锟�锟斤拷匹锟絖锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷藥锟斤拷锟斤拷pH5.0锟侥滲透系锟斤拷(sh锟斤拷)锟紷锟斤拷锟斤拷锟斤拷pH7.4锟斤拷锟斤拷锟斤拷锟斤拷锟藉爾锟斤拷锟斤拷锟斤拷鍫栵拷葔A锟斤拷藥锟斤拷锟斤拷pH7.4锟侥滲透锟斤拷锟紷锟斤拷锟斤拷锟斤拷pH5.0锟斤拷锟斤拷锟紷些藥锟斤拷锟斤拷锟斤拷锟絯锟阶猴拷锟斤拷全锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷锟矫讹拷>90%锟斤拷锟斤拷耍锟絚aco-2锟斤拷(x锟斤拷)锟斤拷試锟�(y锟斤拷n)锟叫撅拷锟紹透锟皆時(sh锟斤拷)锟斤拷锟斤拷锟紹(y锟斤拷ng)锟斤拷锟斤拷pH值锟斤拷(y锟斤拷ng)锟斤拷(d锟斤拷ng)锟斤拷锟絔锟节冿拷(n锟斤拷i)锟侥★拷caco-2锟斤拷(x锟斤拷)锟斤拷锟斤拷(sh锟斤拷)锟�(y锟斤拷n)锟絤锟斤拷锟斤拷锟节憋拷锟斤拷(d锟斤拷ng)锟紻(zhu锟斤拷n)锟絓(y锟斤拷n)锟斤拷藥锟斤拷锟斤拷锟斤拷锟斤拷(du锟斤拷)锟节撅拷锟斤拷锟斤拷锟斤拷(d锟斤拷ng)锟紻(zhu锟斤拷n)锟絓(y锟斤拷n)锟紺(j锟斤拷)锟狡碉拷藥锟斤拷锟斤拷裕锟絚aco-2锟斤拷(x锟斤拷)锟斤拷锟斤拷(sh锟斤拷)锟�(y锟斤拷n)锟紷锟矫的低滲透锟皆結(ji锟斤拷)論锟酵曪拷(hu锟斤拷)锟斤拷(d锟斤拷o)锟铰硷拷锟斤拷锟斤拷袛锟�锟斤拷锟斤拷锟絕锟竭帮拷锟絊锟斤拷锟斤拷锟斤拷D(zhu锟斤拷n)锟絓(y锟斤拷n)锟絯锟斤拷锟斤，锟組锟斤拷锟斤拷caco-2锟紹透锟皆碉拷锟斤拷锟斤拷锟絯锟斤拷(n锟斤拷i)锟斤拷锟斤拷锟斤拷全锟斤拷同锟絩(sh锟斤拷)锟斤拷锟斤拷(du锟斤拷)锟統锟斤拷锟斤拷藥锟斤拷锟杰斤拷使锟矫碉拷DMSO锟斤拷锟斤拷锟紹(y锟斤拷ng)锟斤拷锟叫筹拷锟絕1%锟絩(sh锟斤拷)锟斤拷锟酵曪拷(hu锟斤拷)影锟絚aco-2锟斤拷(x锟斤拷)锟斤拷膜锟侥緊锟斤拷锟紹锟斤拷锟斤拷使锟斤拷锟斤拷F(xi锟斤拷n)锟斤拷锟斤拷越Y(ji锟斤拷)論锟斤拷锟斤拷锟斤拷影響硷拷(x锟斤拷)锟斤拷锟給锟斤拷锟紹锟斤拷锟斤拷锟斤拷锟皆碉拷還锟斤拷锟斤拷藥锟斤拷锟斤拷锟斤拷锟斤拷(x锟斤拷)锟斤拷锟斤拷锟紹(y锟斤拷ng)锟絣锟斤拷锟饺ｏ拷锟斤拷同锟斤拷(sh锟斤拷)锟�(y锟斤拷n)锟斤拷之锟絞锟侥結(ji锟斤拷)锟斤拷锟斤拷锟斤拷锟統锟斤拷锟截現(xi锟斤拷n)锟斤拷

 

 

锟斤拷之锟斤拷锟斤拷锟斤拷藥锟絖锟絣(f锟斤拷)锟絕锟斤拷锟斤拷锟斤拷锟絆(ji锟斤拷n)锟杰機(j锟斤拷)锟斤拷(g锟斤拷u)锟斤拷(du锟斤拷)锟斤拷BE锟斤拷锟斤拷膶锟斤拷锟竭€锟角猴拷謹(j锟斤拷n)锟斤拷锟斤拷锟斤拷锟斤拷悉FDA锟斤拷锟斤拷藥锟斤拷锟�(b锟斤拷o)锟侥岋拷锟斤拷锟斤拷透露锟斤拷锟斤拷锟斤拷锟斤拷(gu锟斤拷)要锟紺锟斤拷一锟斤拷(g锟斤拷)藥锟斤拷母邼B透锟斤拷锟斤拷锟斤拷墓锟斤拷锟斤拷锟斤拷锟斤拷M(f锟斤拷i)锟斤拷也锟斤拷锟斤拷锟斤拷一锟斤拷(g锟斤拷)BE锟斤拷锟斤拷锟斤拷锟斤拷(gu锟斤拷)锟斤拷锟斤拷锟斤拷通锟节凤拷锟狡勶拷锟侥凤拷锟斤拷藥锟斤拷锟斤拷通锟絕BE锟斤拷锟斤拷锟斤拷锟斤拷锟斤拷锟揭囷拷(gu锟斤拷)锟斤拷锟斤拷通锟斤拷锟絯锟节凤拷锟狡勶拷锟斤拷希锟斤拷BE锟斤拷锟斤拷锟斤拷要锟絝锟斤拷CFDA也同锟接诧拷锟阶★拷