IProlastin-C

IProlastin-C

Igama lesiqhelo: I-alpha1-proteinase inhibitor (yabantu)
Ifomu yesisindo: inaliti, isisombululo
Udidi lweziyobisi: Izinto zokuphefumla ezahlukeneyo

By Uhlaziyo lweMedia; Ukuhlaziywa ngu-Varixcare.cz. Igqityelwe ukuhlaziywa ngoMeyi 1, 2021.

Kweli Phepha
Yandisa

Iimpawu kunye nokusetyenziswa kweProlastin-C

IPROLASTIN®-C LIQUID yiAlfa1-Iproteinase Inhibitor (yoLuntu) (Alpha1-PI) ibonakalisiwe ukunyusa okungapheliyo kunye nonyango lokugcina kubantu abadala abanobungqina beklinikhi ye-emphysema ngenxa yokusilela kakhulu kwilifa1-PI (alpha1Ukusilela kwe-antitrypsin).



Imida yokuSetyenziswa

  • Iziphumo zokongezwa kwonyango kuyo nayiphi na iAlfa1-PI, kubandakanya iProlastin-C LIQUID, kwi-pulmonary exacerbations kunye nokuqhubela phambili kwe-emphysema kwiAlfa1Ukusilela kwe-PI akubonakaliswanga ngokucacileyo kwizilingo zeklinikhi ezilawulwa ngokungekho mthethweni.
  • Idatha yeklinikhi ebonisa iziphumo zexesha elide zokunyusa okungapheliyo okanye unyango lokugcina ngeProlastin-C LIQUID azifumaneki.
  • Iprolastin-C LIQUID ayiboniswanga njengonyango lwesifo semiphunga kwizigulana ezineAlfa eqatha1Ukusilela kwe-PI akukhange kusekwe.

Prolastin-C Isikali kunye noLawulo

Ukusetyenziswa kwe-intravenous kuphela.

Ithamo

  • Idosi ekucetyiswa ukuba yiProlastin-C LIQUID ngama-60 mg / kg ubunzima bomzimba obulawulwa ngemithambo kanye ngeveki.

  • Izifundo zethamo eziqala ekusebenziseni indawo yokuphela kokusebenza azange zenziwe ngayo nayiphi na iAlfa1-PI imveliso.

  • Ibhokisi kunye nelebheli kwibhotile nganye yeProlastin-C LIQUID ibonisa elona xabiso lokusebenza kweAlfa esebenzayo1-PI ngeemiligram (njengoko kumiselwe ngumthamo wokunciphisa i-porcine pancreatic elastase).

Ukulungiselela nokuPhatha

  1. Vumela i-Prolastin-C LIQUID ukuba ifudumale iqondo lobushushu kwigumbi ngaphambi kolawulo.
  2. Susa i-flip top top kwi-vial.
  3. Swab umphezulu wokumisa obonakalisiweyo ngotywala kwaye uvumele ukuba wome.
  4. Hlola iProlastin-C LIQUID ngokubonakalayo kwimiba yamasuntswana kunye nombala ngaphambi kokudityaniswa. Imveliso inokuthi iqulethe iiprotheni ezimbalwa. Isisombululo sicacile, singenambala okanye sinombala omthubi okanye umbala oluhlaza. Sukuyisebenzisa ukuba imveliso inombala okanye inamafu.
  5. Pool Prolastin-C LIQUID ukusuka kwiibhotile ezininzi ukufezekisa idosi / kg yomzimba obunzima bomzimba kwisikhongozeli esingenanto, esisinyanzelo sokufaka isisombululo esisebenzisa ubuchule be-aseptic.
  6. Gcina isisombululo esidityanisiweyo kubushushu begumbi kulawulo ngaphakathi kweeyure ezintathu.
  7. Lahla isahlulo esingasetyenziswanga.

Ulawulo

  • Jonga ngokubonakalayo iimveliso zeziyobisi zabazali malunga nomba othile kunye nokujika umbala ngaphambi kolawulo, ngalo lonke ixesha isisombululo kunye nemvume yesikhongozeli. Imveliso inokuthi iqulethe iiprotheni ezimbalwa. Sukuyisebenzisa ukuba ibala nebala okanye kunamafu.
  • Icebo lokucoca ulwelo ngecebo lokucoca ulwelo ngecebo lokucoca ulwelo nge-intravenous set set with a 5 to 15 micron infusion filter (ayinikiwanga).
  • Fakela iProlastin-C LIQUID ngokwahlukeneyo, ngaphandle kokuxubana nezinye iiarhente okanye izisombululo zokunciphisa.
  • Fakela iProlastin-C LIQUID ngaphakathi ngaphakathi nge-0.08 mL / kg / min njengoko kumiselwe yimpendulo yesigulana kunye nentuthuzelo. Umthamo ocetyiswayo we-60 mg / kg uthatha malunga nemizuzu eli-15 ukufaka.

Iifom zedosi kunye namandla

Iprolastin-C LIQUID sisisombululo senaliti esine-500 mg (10 ml), 1,000 mg (20 mL), kunye ne-4,000 mg (80 mL) kwiibhotile zedosi enye. Elona xabiso leAlfa esebenzayo1-PI ngeemiligram iprintwe kwileyibhile yebhokisi nakwibhokisi.

Igama lokurhweba ngeheparin

Ukungqinelana

IProlastin-C LIQUID iyaphikiswa kwi:

  • Izigulana ezinengxaki ye-IgA ene-antibodies ngokuchasene ne-IgA, ngenxa yomngcipheko we-hypersensitivity.
  • Izigulana ezinembali ye-anaphylaxis okanye enye indlela enobuzaza yokusabela kuAlfa1-PI.

Izilumkiso kunye nokuQapha

Ukuphendula gwenxa

Impendulo ye-Hypersensitivity, kubandakanya i-anaphylaxis, inokwenzeka. Jonga iimpawu ezibalulekileyo kwaye ujonge isigulana ngononophelo kulo lonke ukumnika. Iimpawu zokuqala kunye neempawu zokuthintelwa kwe-hypersensitivity zingabandakanya ipruritus; urticaria ngokubanzi; ukugungxula; Ukudumba imilebe, ulwimi, okanye uvule; ukuvutha; ukuqina kwesifuba; idyspnea; uxinzelelo lwegazi; kunye ne syncope. Ukuba iimpawu ze-hypersensitivity ziyenzeka, yeka ukumnika i-Prolastin-C LIQUID ukumiliselwa kwaye uqalise ngonyango olufanelekileyo. Unayo i-epinephrine kunye nolunye unyango olufanelekileyo kunyango lwaso nasiphi na isifo se-anaphylactic okanye se-anaphylactoid reaction.[Bona Ulwazi loLuleko ngeMonde (17) ]

Iprolastin-C LIQUID inokuba nexabiso le-IgA. Izigulana ezinee-antibodies ezaziwayo kwi-IgA, ezinokubakho kwizigulana ezinesiphene esikhethiweyo okanye esibi se-IgA, zinomngcipheko omkhulu wokukhula kwe-hypersensitivity enokwenzeka kunye nokusabela kwe-anaphylactic.

IiAgents eziSuleliyo eziDlulayo

Kuba iProlastin-C LIQUID yenziwe ngeplasma yabantu, inokuba semngciphekweni wokuhambisa ii-arhente ezosulelayo, umzekelo, iintsholongwane, iarhente yesifo seCreutzfeldt-Jakob (vCJD), kwaye, ithiyori, iarhente yesifo seCreutzfeldt-Jakob (CJD). Oku kukwasebenza nakwiintsholongwane ezingaziwayo okanye ezisakhulayo kunye nezinye izifo. Umngcipheko wokudluliselwa kweearhente ezosulelayo uye wancitshiswa ngokuthi kuhlolwe abanikeli beplasma ukuze babonakaliswe ngaphambi kwexesha kwizinto ezithile ezosulelayo, ngokuvavanya ubukho bentsholongwane ethile, nangokubandakanya amanyathelo enkqubo yokwenza kunye namandla abonakalisiweyo okungasebenzi kunye / okanye ukususa izinto ezithile ezosulelayo. Ngaphandle kwala manyathelo, le mveliso isenokudlulisela izifo.

Xela lonke usulelo olucingwa ngugqirha ekusenokwenzeka ukuba lwadluliselwa yile mveliso kwiGrifols Therapeutics LLC (1-800-520-2807).

Iziphumo ezingalunganga

Eyona mpendulo imbi kakhulu ebonwe ngexesha lovavanyo lweklinikhi kunye neProlastin-C yayisisisu esiswini kunye nesiphelo kwisifundo esinye.[Bona Izilumkiso kunye noKhuseleko (5.1) ]

Ezona mpawu zixhaphakileyo ziqwalaselweyo kwinqanaba le-5% kwizifundo ezifumana iProlastin-C LIQUID yayisisifo sorhudo kunye nokudinwa, nganye nganye yenzeke kwinqanaba le-6% (izifundo ezimbini nganye).

Amava ovavanyo lweklinikhi

Kungenxa yokuba izifundo zeklinikhi ziqhutywa phantsi kweemeko ezahluka-hlukeneyo, amaqondo okungafaniyo okuphenduliweyo anokuqwalaselwa ngokuthe ngqo kumaxabiso kwezinye izilingo zeklinikhi kwaye ayinakho ukubonakalisa amaxabiso abonwe ngokwenziwa.

Olunye uvavanyo lweklinikhi lwaluqhutywa ngeProlastin-C LIQUID: iveki ye-16, i-multicenter, i-randomized, i-crossover yokufunda kabini ukuvavanya ukhuseleko, i-immunogenicity, kunye nokuthelekiswa kwe-pharmacokinetic yeProlastin-C LIQUID ukuya kwiProlastin-C kwizifundo ezingama-32.

Iziphumo ezingalunganga (njengoko kuchaziwe kumbhalo osemazantsi ku Itheyibhile 1 ) ezenzeka kwi> 5% yezifundo ngexesha le-16 leveki unyango olungaboniyo olubonisiweyo Itheyibhile 1 .

Itheyibhile 1: Iziphumo ezingalunganga ezenzeka kwi-5% yezifundo ngexesha loNyango lweCrossover eBoniweyo
*
Impendulo egwenxa ichazwa njengaso nasiphi na isiganeko esibi esenzeke apho a) umsitho awuthathelwanga ngoyaba ngokunxulumene nolawulo lwemveliso, okanye b) isenzeko senzeka ngexesha okanye ngaphakathi kweeyure ezingama-72 zokuphela kokungeniswa kwangaphambili kwemveliso, okanye c) uvavanyo lomsindisi womsitho ubungekho okanye ungagqitywanga, okanye d) izehlo ngexesha lonyango ngemveliso yophando e-1 yayiyi-130% okanye nangaphezulu kweziganeko ngexesha lonyango kunye nenye imveliso yophando.
& ikrele;
Umthombo: ulingo lokuthelekisa okungafunekiyo oluphindwe kabini lweProlastin-C LIQUID vs Prolastin-C.
IPROLASTIN®-C LIQUID
(N = 32)
IPROLASTIN®-C
(N = 31)
Ukuphendula okungalunganga * , & ikrele; Inqaku lezifundo ezinokusabela okungalunganga
(ipesenti yazo zonke izifundo)
Inqaku lezifundo ezinokusabela okungalunganga
(ipesenti yazo zonke izifundo)
Urhudo 2 (6) 0
Ukudinwa 2 (6) 0

Itheyibhile 2 Apha ngezantsi kubonisa impendulo engalunganga (echazwe ngokwe Itheyibhile 1 ) njengepesenti ye-infusions efunyenwe ngexesha le-16 leeveki zonyango.

Itheyibhile 2: UkuHamba ngokuSabela okuGwenxa njengepesenti yazo zonke ii-Infusions kunye neZenzeka ngaphezu kwesihlandlo esinye kwi-PROLASTINIqela le-®-C LIQUID ngexesha le-16 leVeki yoNyango oluMfama kabini
*
Umthombo: ulingo lokuthelekisa okungafunekiyo oluphindwe kabini lweProlastin-C LIQUID vs Prolastin-C.
IPROLASTIN®-C LIQUID
I-infusions: 252
IPROLASTIN®-C
Inani lokungeniswa: 245
Ukuphendula okungalunganga * Yeempendulo eziGwenxa
(ipesenti yazo zonke iimpembelelo)
Yeempendulo eziGwenxa
(ipesenti yazo zonke iimpembelelo)
Urhudo 3 (1.2) 0
Ukudinwa 2 (0.8) 0

Inani lilonke le-23 ye-COPD exacerbation iye yaxelwa kwizifundo ezili-18 zizonke. Izifundo ezilishumi elinambini (12/32, 38%) ngexesha lonyango lwe-Prolastin-C LIQUID yafumana ukwanda kwe-13 COPD, kunye nezifundo ezili-9 (9/31, 29%) ngexesha lonyango lweProlastin-C zazine-10 ze-COPD. Ukonyuka okuthathu kweCOPD kwenzeka ngexesha lokuLandela emva kokuba unyango lweProlastin-C LIQUID kunye nokunyanzelwa kwe-1 COPD kwenzeka kwixesha lokulandela emva konyango lweProlastin-C. Ireyithi iyonke yokuxakeka kwepmmonary ngexesha lonyango kunye nokuba yeyiphi na imveliso yayingu-1.9 wokukhula kwisifundo ngasinye ngonyaka. Akukho kucaphuka kwathathwa njengokubi, ngaphandle kwesiganeko esinye emva konyango lweProlastin-C ngexesha lokuLandela (ngenxa yokulaliswa esibhedlele).

Izilingo ezimbini ezahlukileyo zangaphambi kokuqhutywa kweklinikhi zenziwa ngeProlastin-C: 1.) iveki engama-20, ileyibhile evulekileyo, isifundo sokukhusela ingalo enye kwizifundo ezingama-38 (ulingo lwengalo enye evulekileyo), kunye no-2. blind-blind, crossover pharmacokinetic yokufunda ukuthelekisa vs.PROLASTIN kwizifundo ezingama-24, kulandelwa unyango lweelebheli ezivulekileyo nge-8 ngeProlastin-C. Ke, izifundo zizonke ezingama-93 zavezwa kwiProlastin-C kuvavanyo lweklinikhi.

Eyona mpendulo imbi kakhulu ebonwe ngexesha lovavanyo lweklinikhi kunye neProlastin-C yayisisisu esiswini kunye nesiphelo kwisifundo esinye. Irhashalala isonjululwe emva kokunyanga ngaphandle kwe-antihistamines kunye ne-steroids. Iziganeko ezibini zesifo esinganyanzelekanga kangako, ukurhaba kwamazantsi esisu kwaqwalaselwa kwirengalenge ngaphandle kokuqhubeka nokunyanga i-antihistamine kunye nonyango lwe-steroid, olukhokelele ekurhoxisweni komxholo kulingo.

Iigrifols kuvavanywe ulingo lokuthelekisa okungaboniyo lwePROLASTIN kunye neProlastin-C yokuphendula okungalunganga (njengoko kuchaziwe kumbhalo osemazantsi Itheyibhile 3 ) ezenzeka ngexesha leeveki ezisi-8 zonyango olwenziwe kabini, njengoko kubonisiwe Itheyibhile 3 .

Itheyibhile 3: Iziphumo ezingalunganga ezenzeka kwiiveki zokuqala ezi-8 zonyango ngalunye olwenziwe iimfama
*
Impendulo egwenxa ichazwa njengaso nasiphi na isiganeko esibi apho a) Isigameko seProlastin-C sasisikhulu kunePROLASTIN, okanye b) Isenzeko sasingaphakathi kweeyure ezingama-72 zonyango, okanye c) umsitho wawuthathwe ngenye indlela unxulumene okanye mhlawumbi unxulumene iyeza.
& ikrele;
Umthombo: ulingo lokuthelekisa olumfamekileyo olungenamsebenzi.
IPROLASTIN®-C
Inani lezifundo: 24
IPROLASTIN®
Inani lezifundo: 24
Ukuphendula okungalunganga * , & ikrele; Inqaku lezifundo ezinokusabela okungalunganga
(ipesenti yazo zonke izifundo)
Inqaku lezifundo ezinokusabela okungalunganga
(ipesenti yazo zonke izifundo)
Usulelo oluphezulu lokuphefumula 3 (12.5%) 1 (4.2%)
Intloko ebuhlungu 1 (4.2%) 2 (8.3%)
Pruritus 1 (4.2%) 0
Urticaria 1 (4.2%) 0
Isicaphucaphu 1 (4.2%) 0
Ukudumba kwemida 1 (4.2%) 0
IPyrexia 1 (4.2%) 0

Itheyibhile 4 Apha ngezantsi kubonisa impendulo engalunganga (echazwe ngokwe Itheyibhile 3 ) njengepesenti ye-infusions efunyenwe ngexesha leeveki ezisi-8 zonyango ngalunye oluphindwe kabini.

Itheyibhile 4: Ubuninzi bokusabela okungalunganga njengepesenti yazo zonke izinto ezikhuthazayo ngexesha leeveki ezisi-8 zokuqala kunyango ngalunye lokungeniswa okungaboniyo
*
Umthombo: ulingo lokuthelekisa olumfamekileyo olungenamsebenzi.
IPROLASTIN®-C
I-infusions: 188
IPROLASTIN®
I-infusions: 192
Ukuphendula okungalunganga * Yeempendulo eziGwenxa
(ipesenti yazo zonke iimpembelelo)
Yeempendulo eziGwenxa
(ipesenti yazo zonke iimpembelelo)
Usulelo oluphezulu lokuphefumula 3 (1.6%) 1 (0.5%)
Intloko ebuhlungu 1 (0.5%) 3 (1.6%)
Pruritus 1 (0.5%) 0
Urticaria 1 (0.5%) 0
Isicaphucaphu 1 (0.5%) 0
Ukudumba kwemida 1 (0.5%) 0
IPyrexia 1 (0.5%) 0

Uluhlu 5 Apha ngezantsi kubonisa iimpendulo ezigwenxa ezenzeka kwizifundo ezibini okanye nangaphezulu ngexesha lokulingwa kwelebheli engalulo.

Itheyibhile 5: Ukujongana okungalunganga okwenzeka kwiZifundo eziBini okanye eziNinzi (> 5%) ngexesha leSilingo samaLungu angama-20 seLungu elinye leLebhu evulekileyo
*
Impendulo egwenxa ichazwa njengaso nasiphi na isiganeko esibi esenzekileyo apho a) Isenzeko sasikwiiyure ezingama-72 zonyango, okanye b) umsitho wawuthathwe ngenye indlela unxulumene okanye unxulumene nesiyobisi.
& ikrele;
Umthombo: ingalo enye, uvavanyo lweelebhile ezivulekileyo.
IPROLASTIN®-C
Inani lezifundo: 38
Ukuphendula okungalunganga * , & ikrele; Inqaku lezifundo ezinokusabela okungalunganga
(ipesenti yazo zonke izifundo)
Usulelo oluphezulu lokuphefumula I-6 (15.8%)
Usulelo lwe-Urinary tract I-5 (13.2%)
Isicaphucaphu 4 (10.5%)
Iintlungu zesifuba Isi-3 (7.9%)
Umqolo obuhlungu 2 (5.3%)
Ukugodola 2 (5.3%)
Khohlela 2 (5.3%)
Ukuba nesiyezi 2 (5.3%)
IDyspnea 2 (5.3%)
Intloko ebuhlungu 2 (5.3%)
Ukutshisa okushushu 2 (5.3%)
I-candidiasis yomlomo 2 (5.3%)

Ukunyanzelwa kweshumi kwesifo esinganyangekiyo semiphunga kuxelwe kwizifundo ze-8 kwiveki ye-24 ye-crossover pharmacokinetic Study. Ngexesha le-16 yeveki ye-crossover ephindwe kabini, izifundo ze-4 (17%) zazine-4 exacerbation ngexesha lonyango lwe-Prolastin-C kunye nezifundo ze-4 (17%) ezazine-4 exacerbations ngexesha lonyango lwe-PROLASTIN. Ukunyuka okongeziweyo okubini kwizifundo ze-2 (8%) kwenzeka ngexesha leeveki ezisi-8 lonyango oluvulekileyo lwelebheli kunye neProlastin-C. Ireyithi iyonke yokuxakeka kwepmmonary ngexesha lonyango kunye nokuba yeyiphi na imveliso yayingu-0.9 yokunyuka kwisifundo ngasinye ngonyaka.

Ukuzikhusela

Ukufunyanwa kolwakhiwo lwe-antibody kuxhomekeke kakhulu kubuntununtunu kunye nokubalulwa kwe-assay. Ukongeza, imeko ye-antibody (kubandakanya ne-anti-anti-anti-anti) yokuziva unomdla kwi-assay inokuchaphazeleka kwizinto ezininzi kubandakanya indlela yokuvavanywa, ukuphathwa kwesampulu, ixesha lokuqokelelwa kwesampulu, amayeza ahambelanayo, kunye nesifo esisisiseko. Ngenxa yezi zizathu, ukuthelekiswa kweziganeko ze-antibodies kunye neProlastin-C LIQUID kunye neziganeko ze-antibodies kwezinye iimveliso zingalahlekisa.

Kwilingo elingenamkhethe, le-crossover pharmacokinetic yecala leklinikhi, akukho mpendulo ye-immunogenicity eyaqwalaselwa kwizifundo ezichongwe ngeProlastin-C LIQUID okanye iProlastin-C.

Kwingalo enye, uvavanyo lweklinikhi evulekileyo yovavanyo lwezonyango, izifundo zonyango ezintathu ze-naïve kwizifundo ezingama-36 kuvavanyo lwe-antibody e-Alpha1-PI ngeveki yama-24 emva kokufumana iProlastin-C. Isifundo sesine (esinge-naïve) sasinethemba ngaphambi nasemva kokufumana iProlastin-C, kodwa amanqanaba awatshintshanga ngexesha lokufunda. Akukho nanye kwezi zine ze-antibody ikwazileyo ukunciphisa ubungakanani be-protease inhibitor yeProlastin-C. Kwilingo elingenamkhethe, le-crossover pharmacokinetic yecala lekliniki ngokuthelekisa iProlastin-C kunye ne-PROLASTIN, akukho nasinye kwezifundo ezingama-24 ezenze izilwa-buhlungu kwiProlastin-C.

Amava entengiso

Kuba ukuthengisa emva kokumakishwa kweempendulo kukungaziphathi ngokuzithandela kwaye kubemi abanobungakanani obungaqinisekanga, akusoloko kunokwenzeka ukuba uqikelele ngokuthembekileyo ubukhulu bezi mpendulo okanye useke ubudlelwane obunobangela wokuvezwa kwemveliso.

Amava alindelweyo okuthengisa emva kwexesha kwintengiso yeProlastin-C LIQUID isekwe kwiimpendulo ezichazwe kwiProlastin-C. Iimpendulo ezikhethelwe ukufakwa ngenxa yobuzaza bazo, ukuphindaphindwa kokwenza ingxelo, unxibelelwano olunokubangela i-PROLASTIN®-C, okanye indibaniselwano yezi zinto, zezi:

  • Ngokubanzi / ngeQumrhu lilonke:Ukudinwa, ukubola, isifo esifana nomkhuhlane, iintlungu, i-asthenia
  • Inkqubo yomzimbaHypersensitivity kubandakanya ukuphendula kwe-anaphylactoid / anaphylactic
  • Intliziyo:Tachycardia
  • Imisipha:Arthralgia, myalgia
  • Isisu:Ukugabha, urhudo
  • Uphando:Uxinzelelo lwegazi lwanda

UKUSETYENZISWA KWABANTU ABAKHETHEKILEYO

Ukukhulelwa

Isishwankathelo somngcipheko

Akukho datha ngokusetyenziswa kweProlastin-C LIQUID kwabasetyhini abakhulelweyo ukwazisa umngcipheko onxulumene neziyobisi. Izifundo zokuvelisa izilwanyana azikhange zenziwe ngeProlastin-C LIQUID. Ayaziwa ukuba iProlastin-C LIQUID inokubangela ukwenzakala komntwana xa enikwa umfazi okhulelweyo okanye inokuchaphazela amandla okuzala. IProlastin-C LIQUID kufuneka inikwe owasetyhini okhulelweyo kuphela xa kufuneka ngokucacileyo.

Kubantu base-US ngokubanzi, umngcipheko wokuqikelelwa kwemvelaphi yesiphene sokuzalwa kunye nokuphuphuma kwesisu kukhulelwa okwamkelweyo ngokwezonyango yi-2-4% kunye ne-15-20%, ngokwahlukeneyo.

Lactation

Isishwankathelo somngcipheko

Akukho lwazi malunga nobukho beProlastin-C LIQUID kubisi lomntu, iziphumo kusana olusancanciswa, okanye iziphumo kwimveliso yobisi. Izibonelelo zophuhliso kunye nezempilo zokuncancisa kufuneka ziqwalaselwe kunye neemfuno zikamama zeklinikhi zeProlastin-C LIQUID kunye naziphi na iziphumo ezinokubakho kusana olusancancisayo olusuka kwiProlastin-C LIQUID okanye kwimeko engaphantsi yomama.

Ukusetyenziswa kwabantwana

Ukhuseleko kunye nokusebenza kubemi babantwana akukhange kusekwe.

Ukusetyenziswa kweGeriatric

Izifundo zonyango lweProlastin-C LIQUID khange zibandakanye inani elaneleyo lezifundo ezineminyaka engama-65 nangaphezulu ukufumanisa ukuba baphendula ngokwahlukileyo kwizifundo ezincinci. Ngokumalunga nazo zonke izigulana, iidosi kwizigulana ezinesifo esifanelekileyo kufuneka zilungele imeko yazo iyonke.

Inkcazo yeProlastin-C

Iprolastin-C LIQUID yinyumba, ukugxila kweAlfa1-PI yokumnika ngaphakathi. Isisombululo sicacile, singenambala okanye sinombala omthubi okanye umbala oluhlaza. Elona xabiso leAlfa esebenzayo1-PI ngeemiligram, njengoko kumiselwe ngumthamo wokuphelisa i-porcine pancreatic elastase, iprintwe kwibhokisi kunye nelebhile yentsimbi yeProlastin-C LIQUID. Umsebenzi othile weProlastin-C LIQUID yi ≧ 0.7 mg esebenzayo yeAlfa1-PI ngomg weprotheni iyonke. Iprolastin-C LIQUID inobunyulu be-90% yeAlfa1-PI (Alfa1-PI protein / iyonke protein). Iprolastin-C LIQUID ine-pH eyi-6.6-7.4, umxholo wesodium phosphate we-0.013-0.025 M, kwaye uzinzile nge-0.20-0.30 M ye-alanine. Ubuninzi be-sodium concentration ngu-100 mEq / L. IProlastin-C LIQUID ayiqulathanga kwisigcinakaliso.

Iprolastin-C LIQUID iveliswa kwiplasma yabantu edibeneyo ngokulungiswa kwenkqubo ye-PROLASTIN kusetyenziswa ukucocwa yi-polyethylene glycol (PEG) yemvula, i-anion exchange chromatography, kunye ne-cation exchange chromatography. Yonke imvelaphi yePlasma esetyenziswe ekwenziweni kweProlastin-C LIQUID ayisebenzi (inegasi) ngeendlela zovavanyo lwe-serological ezinelayisensi ye-hepatitis B yomphezulu we-antigen (HBsAg) kunye neentsholongwane zentsholongwane ye-hepatitis C (HCV) kunye neentlobo zentsholongwane yabantu 2 kunye ne-FDA enelayisensi ye-Nucleic Acid Technologies (NAT) enelayisensi ye-FDA ye-HCV kunye ne-virus ye-immunodeficiency type 1 (HIV-1). Ukongeza, yonke iMvelaphi yePlasma ayinayo intsholongwane ye-hepatitis B (HBV) nokuba ilayisenisi ye-FDA okanye uphando lwe-NAT. Injongo yovavanyo lophando lwe-HBV NAT kukufumana amanqanaba asezantsi e-viral nucleic acid; Nangona kunjalo, ukubaluleka kwesiphumo esibi kuvavanyo lwe-HBV NAT yophando akukenziwa. Ngokwenkqubo ye-NAT, yonke iMvelaphi yePlasma ayinayo intsholongwane ye-hepatitis A (HAV). Njengenyathelo lokugqibela lokhuseleko lweplasma, onke amachibi okuvelisa iplasma avavanywa ngeendlela zovavanyo lwe-serological kunye ne-NAT.

Ukuvavanya ngakumbi iprofayili yokhuseleko kwintsholongwane yeProlastin-C LIQUID,i-In vitroIzifundo ziye zaqhutywa ukuqinisekisa ubungakanani benkqubo yokuvelisa ukunciphisa umxholo osulelayo woluhlu olubanzi lweentsholongwane ezineempawu ezahlukeneyo zemichiza. Olu phononongo luvavanye ukungasebenzi / ukususwa kweentsholongwane ezifanelekileyo zeklinikhi, kubandakanya uhlobo lwentsholongwane kaGawulayo (i-HIV-1) kunye ne-hepatitis A virus (HAV), kunye nezi ntsholongwane zilandelayo: intsholongwane hepatitis C; i-virus ye-pseudorabies (PRV), i-surrogate yentsholongwane enkulu ye-DNA (umzekelo, i-herpes virus); i-vesicular stomatitis virus (VSV), imodeli yeentsholongwane ezigubungelweyo; uhlobo lwe-reovirus 3 (Reo3), imodeli engachazwanga yeentsholongwane ezingagutyungelwanga; kunye ne-porcine parvovirus (PPV), imodeli yeparvovirus yabantu B19.

Inkqubo yokuvelisa iProlastin-C LIQUID inamanyathelo aliqela (iCold Ethanol Fractionation, PEG Precipitation, and Depth Filtration) ebalulekileyo ekucoceni iAlfa1-PI kunye nokususa intsholongwane enokubakho. Amanyathelo amabini ongezelelweyo, i-Solvent / Detergent Treatment kunye ne-15 nm ye-Virus Removal Nanofiltration, zibandakanyiwe kwinkqubo njengenyathelo lokuncipha kwentsholongwane. Inyathelo leSolvent / iDetergent Treatment lisebenza ngokungasebenziyo kwiintsholongwane ezigutyungelweyo (ezinje nge-HIV-1, VSV, HBV, kunye ne-HCV). Inqanaba le-15 nm lokususwa kweNtsholongwane liye laphunyezwa ukunciphisa umngcipheko wokudluliselwa kwentsholongwane egutyungelweyo nengagutyungelwanga encinci njenge-18 nm. Itheyibhile 6 iveza inqanaba lokuncitshiswa kwentsholongwane kwinyathelo ngalinye lenkqubo kunye nokuncitshiswa kwentsholongwane okuqokelelweyo kwenkqubo njengoko kumisiwe kwizifundo zokuqinisekiswa kwentsholongwane apho intsholongwane yongezwa ngabom kwimodeli yenkqubo ukuze kufundwe ukunciphisa intsholongwane. Ukongeza, inyathelo lesinyibilikisi / inyango lonyango alisebenzi log 5.4 log10kwintsholongwane yeNayile, intsholongwane egutyungelweyo.

Itheyibhile 6: UkuNcitshiswa kweNtsholongwane (Log10) yePROLASTIN®-C Inkqubo yokuThengiswa kweLidi
Inkqubo yeNyathelo Iintsholongwane ezigutyungelweyo Iintsholongwane ezingafakwanga
Intsholongwane kaGawulayo-1 BVDV INKQUBO VSV Reo3 ULWANDLE I-PPV
*
Akuzimiselwanga. Ukungasebenzi kwe-VSV kunye / okanye ukususwa kwamiselwa kuphela kunyango / isisombululo sonyango kunye ne-15 nm yokususwa kwentsholongwane.
& ikrele;
Ayingeni. Eli nyathelo lisebenza kuphela ngokuchasene neentsholongwane ezigutyungelweyo.
Ukuqhekeka kweCold Ethanol 1.5 1.7 2.5 ND * 2.1 1.4 1.0
Ukuzikisa kwe-PEG 4.3 2.8 3.3 ND 3.3 3.0 3.2
Ubunzulu beFiltration 4.7 4.0 4.8 ND 4.0 2.8 4.4
Unyango lweSolvent / Detergent 6.2 4.6 4.3 5.1 N / A & ikrele; N / A N / A
15 nm Ukususwa kweNtsholongwane 6.9 4.7 5.2 5.1 4.3 5.5 4.2
Ukunciphisa iNtsholongwane 23.6 Ukufika kwi-17.8 ≧ 20.1 10.2 13.7 12.7 12.8

Ukongeza, inkqubo yokuvelisa yaphononongwa ngesakhono sayo sokunciphisa ukusasazeka kwearhente yovavanyo yesifo se-spongiform encephalopathy (TSE), ethathelwa ingqalelo njengemodeli yesifo seCreutzfeldt-Jakob (vCJD) kunye neearhente zesifo seCreutzfeldt-Jakob (CJD). Izifundo zenkqubo yokuvelisa iProlastin-C yeLIQUID ibonisa ukuba ubuncinci be-log ye-610Ukuncitshiswa kokosuleleka kwi-TSE kufezekisiwe. Olu phononongo lubonelela ngesiqinisekiso esifanelekileyo sokuba amanqanaba asezantsi e-vCJD / CJD isifo sokuthintela isifo, ukuba sikhona kwizinto zokuqala, ziya kususwa.

Prolastin-C-Clinical Pharmacology

Indlela yokuSebenza

UAlfa1Ukusilela kwe -PI sisifo esizimeleyo, esilawulayo, isifo esivela kwilifa esichazwa ngamanqanaba asezantsi e-serum kunye nemiphunga yeAlfa1-PI. Ukutshaya yinto ebalulekileyo yomngcipheko kuphuhliso lwe-emphysema kwizigulana ezine-Alpha1Ukusilela -PI. ( 1.2 Kungenxa yokuba i-emphysema ichaphazela abaninzi, kodwa ayingabo bonke abantu abaneempawu ezibi kakhulu zofuzo lweAlfa1Ukusilela -PI, ukunyusa unyango kunye neAlfa1-PI iboniswa kuphela kwizigulana ezineAlfa ebukhali1Ukusilela -PI abane-emphysema ebonakalayo eklinikhi.

Kuphela yiAlfa1Ii-alle ze-PI zinxulunyaniswa ne-Alpha ebonakalayo ekliniki1Ukusilela -PI. ( 3.4 Phantse iipesenti ezingama-95 zazo zonke izigulana eziswele kakhulu zi-homozygous ze-PiZ allele. ( 4 Abantu abanePiZZ eyahlukileyo ngesiqhelo bane-serum Alpha1-PI amanqanaba angaphantsi kwe-35% yenqanaba eliqhelekileyo eliqhelekileyo. Abantu abanePi (null) (null) umahluko baneAlfa engabonakaliyo1-PI protein kwi-serum yabo. Abantu abathile abane-serum ephantsi yeAlfa1Amanqanaba e-PI, okt angaphantsi kwe-11 µM, anomngcipheko ophakamileyo wokukhula kwe-emphysema ngaphezulu kwexesha lokuphila kwabo. Ukongeza, abantu bePiSZ, abane-serum Alpha1Amanqanaba ePI aqala malunga ne-9 ukuya kwi-23 µM, ( 5) zithathwa njengezinomngcipheko ophakathi wokukhula kwe-emphysema, nokuba iyintoni na i-serum Alpha1Amanqanaba e-PI angentla okanye angaphantsi kwe-11 µM.

Ukonyusa amanqanaba okusebenza kweprotease inhibitor ngokufakwa ngaphakathi kungena kunyango kwizigulana ezineAlfa1Ukusilela -PI. Injongo yethiyori kukubonelela ngokhuseleko kumatshini wokuphefumla osezantsi ngokulungisa ukungalingani phakathi kwe-neutrophil elastase kunye ne-protease inhibitors. Nokuba unyango lokwandiswa kunye nayiphi iAlfa1-Imveliso ye-PI iyayikhusela indlela yokuphefumla esezantsi ukusuka kutshintsho oluqhubekayo lwe-emphysematous engakhange iboniswe kumandla aneleyo, alawulwa ngokungenamkhethe, kuvavanyo lweklinikhi. Nangona ukugcinwa kwamanqanaba eserum egazi leAlfa1-PI (umlinganiso we-antigenic) ngaphezulu kwe-11 µM iye yabhalwa ngokwembali ukubonelela ngokhuseleko lwe-anti-neutrophil elastase, ( 6 ) oku akukangqinwa. Abantu abane-Alpha eqatha1Ukusilela kwe -PI kubonisiwe ukuba kwandise i-neutrophil kunye ne-neutrophil elastase ekugxileni1-PI ngaphezulu kwe-11 µM ine-emphysema enxulumene neAlfa1Ukusilela -PI. Oku kuqatshelweyo kugxininisa ukungaqiniseki ngokubhekisele kwinqanaba elifanelekileyo le-serum ekujolise kuyo kunyango1-PI ngexesha lokonyusa unyango.

I-pathogenesis ye-emphysema iyaqondwa njengoko ichaziwe kwimodeli yokungalingani yeprotease-antiprotease. UAlfa1-PI iqondwa njengeyona antiprotease ephambili kwindawo yokuphefumla esezantsi, apho ithintela i-neutrophil elastase (NE). Abantu abaqhelekileyo abasempilweni bavelisa iAlfa eyaneleyo1-PI yokulawula i-NE eveliswe zii-neutrophils ezisebenzayo kwaye ke ziyakwazi ukuthintela iproteolysis engalunganga yethishu yemiphunga nge-NE. Iimeko ezonyusa ukuqokelelwa kwe-neutrophil kunye nokusebenza kwimiphunga, njengosulelo lokuphefumla kunye nokutshaya, kuya kuthi kwandise amanqanaba e-NE. Nangona kunjalo, abantu abathile abanesiphene esiqatha kwi-Alpha engapheliyo1-PI abakwazi ukugcina ukhuselo olufanelekileyo lwe-antiprotease, kwaye, ukongeza, babonakalisile ukuba bandise i-lung epithelial lining fluid neutrophil kunye ne-NE. Ngenxa yezi zinto, uninzi (kodwa ayingabo bonke) abantu abanesiphene esiqatha ku-Alpha ongapheliyo1-PI zixhomekeke kwiproteolysis ekhawulezileyo yeendonga ze-alveolar ezikhokelela kwisifo esingapheliyo semiphunga. IProlastin-C LIQUID isebenza njengeAlfa1Unyango lokwandisa i-PI kubemi abaguli abaneAlfa ebukhali1-Ukusilela kwe-PI kunye ne-emphysema, esebenza ukonyusa kunye nokugcina amanqanaba e-alum alum e-serum kunye ne-lung epithelial lining1-PI.

Pharmacodynamics

Unyango lokwandiswa okungapheliyo kunye nemveliso eyandulelayo, PROLASTIN®Ukulawulwa kweveki ngedosi ye-60 mg / kg ubunzima bomzimba, kukhokelela kwinqanaba lokunyuka kweAlfa1-PI kunye nokusebenza kwe-anti-neutrophil elastase kwi-epithelial lining fluid yendlela esezantsi yokuphefumla, xa kuthelekiswa namanqanaba ngaphambi kokuqala unyango nge-PROLASTIN. ( 7 ).1-PI imveliso.

Iprolastin-C LIQUID inyusa i-antigenic kunye nokusebenza (anti-neutrophil elastase capacity, ANEC) amanqanaba eserum.

Pharmacokinetics

Isifundo se-pharmacokinetic (PK) sasilungiselelwe ngokungalungelelananga, singaboni kabini, uvavanyo lwe-crossover ngokuthelekisa iProlastin-C LIQUID neProlastin-C (Alpha1-Iproteinase Inhibitor [yoLuntu]) eqhutywa kwizifundo zabantu abadala ezingama-32 zeminyaka yobudala engama-44 ukuya kuma-71 iminyaka eneAlfa eqatha1Ukusilela -PI. Izifundo ezilishumi elinesibhozo zazingamadoda kwaye i-14 yezifundo yayingabafazi. Izifundo ezilishumi elinesithandathu zazinokulandelelana ngokulandelelana kwonyango. Zonke ngaphandle kwesifundo esinye sasinePiZZ genotype kwaye isifundo esasisele yayiyiPiSZ. Izifundo ezingamashumi amabini anesibhozo zazifumene ngaphambi kweAlfa1Unyango lokwandiswa kwe-PI kunye nezifundo ze-4 zazingama-alfa1Unyango lokwandiswa kwe-PI. Izifundo ezifundwayo zabelwa ngokungakhethiyo ukuba zifumane i-60 mg / kg yesisindo somzimba seProlastin-C LIQUID okanye iProlastin-C veki nganye ngokufakwa ngaphakathi ngexesha lokunyanga ngeveki ezisi-8. Ukulandela idosi yokugqibela kwithuba lokuqala lonyango lweeveki ezisi-8, izifundo ziye zenziwa isampulu yegazi ngokulandelelana yohlalutyo lwe-PK zaze zawela kolunye unyango lwexesha lesibini leeveki ezisi-8. Ukulandela unyango lokugqibela kwithuba lesibini leeveki ezisi-8 zonyango, izifundo ziye zenziwa isampulu yegazi ngokulandelelana yohlalutyo lwe-PK. Ukongeza, iisampulu zegazi zatsalwa kumanqanaba omkhombe ngaphambi kokufakwa kwiVeki ye-6, 7, 8, kunye ne-9, nangaphambi kokufakwa kwiVeki ye-14, 15, 16, kunye ne-17. iiveki emva kwedosi yokugqibela) ukulungisa i-Alpha engapheliyo1Amanqanaba -PI.

Ipharamitha ephambili ye-pharmacokinetic yayiyindawo ephantsi kwe-serum Alpha1-I-concentration ye-anti-anti-anti-time curve (AUC0-7days) ukulandela unyango lweeveki ezisi-8 ngeProlastin-C LIQUID okanye iProlastin-C. Ixesha lokuzithemba le-90% (1.03-1.08) yomlinganiso we-AUC0-7daysIprolastin-C LIQUID kunye neProlastin-C zibonise ukuba ezi mveliso zimbini ziyalingana, okt lonke uluhlu luwela phakathi kwe-0.80 - 1.25 yexesha. I-AUC0-7daysyealfa elingana ne-serum1Uxinzelelo lwe -PI ngovavanyo olusebenzayo kunye no-Cubuninzingovavanyo lwe-antigenic kunye nokusebenza kunike iziphumo ezifanayo kwiProlastin-C LIQUID kunye neProlastin-C, njengoko kubonisiwe kwi Itheyibhile 7 .

Itheyibhile 7: Iziphumo zoVavanyo lweNkcukacha manani lweParamacokinetic Parameters eSteady-State (PK Population)
Unyango I-AUC0-7days(mg * h / ml)
Umxholo we-Antigenic Umsebenzi wokuSebenza
Ijiyometri
NGO
Ijiyometri
Ratio
I-90% CI ye
Ijiyometri
Ratio
Ijiyometri
NGO
Ijiyometri
Ratio
I-90% CI ye
Ijiyometri
Ratio
IPROLASTIN®-C
I-LIQUID n = 30
203.57 1.05 1.03, 1.08 169.86 1.04 1.01, 1.07
IPROLASTIN®-C
n = 28
193.71 163.52
Unyango Cubuninzi(mg / ml)
IPROLASTIN®-C
I-LIQUID n = 30
2,517 1.04 1.00, 1.09 2,062 1.04 1.00, 1.07
IPROLASTIN®-C
n = 28
2,415 1,992

Isiqingatha sobomi (t1/2Umxholo we-antigenic wawuthelekiswa, ngakumbi iiyure ezili-156.39 xa kuthelekiswa neeyure ezili-164.10 zeProlastin-C LIQUID xa kuthelekiswa neProlastin-C, ngokwahlukeneyo. Isiqingatha sobomi esifanayo saqwalaselwa kwakhona xa kuvavanywa umsebenzi osebenzayo phakathi kweProlastin-C LIQUID xa kuthelekiswa neProlastin-C (iiyure ezili-126.57 xa kuthelekiswa neeyure ezili-126.82 ngokwahlukeneyo).

Umzobo 1 ibonisa uxinzelelo olulinganayo lwe-serum (umsebenzi osebenzayo) vs.1-PI emva kolawulo lwe-intravenous lweProlastin-C LIQUID kunye neProlastin-C.

Umzobo 1: Kuthetha iAlfa efanayo ne-Serum1-Ukuxinana kwe-PI (imisebenzi esebenzayo) vs.Iejika zeeXesha elilandela unyango ngePROLASTIN®-C LIQUID okanye PROLASTIN®-C

Amanqanaba omkhombe weSerum alinganiselwe kwimeko yozinzo ngexesha lofundo lwe-PK kusetyenziswa umxholo we-antigenic obonisa ukuba iProlastin-C LIQUID ikhokelele kumkhombe we-17.7 µM kunye nePROLASTIN- kunye neentloni; C ikhokelele kumkhombe we-16.9 µM.

Isifundo esingahleliwe, esingaboniyo kabini, esenziwe nge-crossover pharmacokinetic (PK) ngokuthelekisa iProlastin-C kunye nePROLASTIN yenziwa kwizifundo zabantu abadala ezingama-24 ukuya kwiminyaka engama-72 nge-Alpha eqatha1Ukusilela -PI. Izifundo ezilishumi zazingamadoda kwaye i-14 yezifundo yayingabafazi. Zonke ngaphandle kwesifundo esinye sasinePiZZ genotype kwaye isifundo esasinePiSZ. Zonke izifundo zazifumene ngaphambi kweAlfa1Unyango lwe-PI ngePROLASTIN okungenani inyanga enye. Isahlulo esingaboniyo kabini sophando senziwe ngendlela efanayo ne-randomized, blind-blind, crossover PK yokufunda ngokuthelekisa iProlastin-C LQUID neProlastin-C echazwe apha ngasentla.

Iparacokinetic parameter yeAlfa1-PI kwiplasma, esekwe kulingo olulinganayo lomsebenzi we-serum, ibonise ukuthelekiswa phakathi konyango lweProlastin-C kunye nonyango lwePROLASTIN, njengoko kubonisiwe Itheyibhile 8 .

Itheyibhile 8: IParamacokinetic Parameters zeAlfa1-PI kwiPlasma
Unyango I-AUC0-7 iintsuku
(hr * mg / ml)
Kuthetha (% CV)
Cubuninzi
(mg / ml)
Kuthetha (% CV)
t1/2
(hr)
Kuthetha (% CV)
IPROLASTIN®-C
(n = 22 okanye 23)
155.9
(17%)
1,797
(10%)
146.3
(16%)
IPROLASTIN®
(n = 22 okanye 23)
152.4
(16%)
1,848
(Shumi elinantlanu%)
139.3
(18%)

Ipharamitha ephambili ye-pharmacokinetic yayiyindawo ephantsi kweplasma Alpha1-I-concentration ye-anti-anti-anti-time curve (AUC0-7days) emva kweeveki ezisi-8 zonyango kunye neProlastin-C okanye iProlastin. Ixesha lokuzithemba le-90% (0.97-1.09) kumlinganiso we-AUC0-7daysyeprolastin-C kunye nePROLASTIN ibonakalise ukuba iimveliso ezi-2 ziyalingana, okt lonke uluhlu luwela ngaphakathi kwe-0.80 - 1.25% yexesha.

Amanqanaba alinganayo eserum alinganiswa ngexesha lokufunda kwe-crossover PK kusetyenziswa umxholo we-antigenic obonisa ukuba unyango lweProlastin-C lubangele umkhombe we-16.9 ± 2.3 µM kunye nePROLASTIN kukhokelela kumkhombe we-16.7 ± 2.7 µM. Sebenzisa uvavanyo lomsebenzi osebenzayo, iProlastin-C ikhokelele kumkhombe we-11.8 ± 2.2 µM kunye nePROLASTIN kukhokelela kumkhombe we-11.0 ± 2.2 µM.

Unclinical Toxicology

ICarcinogenesis, iMutagenesis, ukungasebenzi kakuhle kokuchuma

I-Carcinogenesis, i-mutagenesis, kunye nokuphazamiseka kwezifundo zokuchuma azange zenziwe; Iprolastin-C LIQUID yibhayoloji ehlanjululwe kwiplasma yomntu.

I-Toxicology yezilwanyana kunye / okanye i-Pharmacology

Ukufakwa ngaphakathi kwemithamo emihlanu yemihla ngemihla yeProlastin-C LIQUID kwimivundla yethamo ukuya kuthi ga kwi-600 mg / kg ngemini (idosa eliphindwe kalishumi kunedosi ekhuthazwayo yomntu eyi-60 mg / kg elawulwa ngeveki), khange kubekho zimpawu yetyhefu. Ukongeza, kwakungekho mahluko kukhuseleko kunye nokunyamezelana kweProlastin-C kunye neProlastin-C LIQUID kuvavanyo olungelulo.

Izifundo zonyango

Ukusebenza kweeklinikhi kweProlastin-C LIQUID ekuphembeleleni ikhosi ye-pulmary emphysema okanye i-pulmonary exacerbations ayiboniswanga kuxhotyiso olwaneleyo, olungenamkhethe, olulawulwayo lwezonyango.

Itotali yezifundo ze-23 ezine-PiZZ eyahlukileyo kunye ne-emphysema ebhaliweyo yafundwa ngengalo enye, ilayibhile evulekileyo yovavanyo lweklinikhi ngePROLASTIN, imveliso eyandulelayo. Ishumi elinethoba lezifundo zifumene i-PROLASTIN, 60 mg / kg, kanye ngeveki ukuya kuthi ga kwiiveki ezingama-26 (i-avareji yeeveki ezingama-24). Amanqanaba egazi eAlfa1-PI zigcinwe ngaphezulu kwe-11 µM. Izifundo zokuhlanjwa kwe-Bronchoalveolar zibonise ngokonyuka kwamanani okonyuka kweAlfa1-PI kunye nokusebenza kwe-ANEC kwi-epithelial lining fluid yendlela esezantsi yokuphefumla yemiphunga, xa kuthelekiswa namanqanaba ngaphambi kwedosi.

Ukongeza kuvavanyo lweProlastin-C LIQUID / Prolastin-C echazwe apha ngasentla, apho izifundo ezingama-31 zafumana iProlastin-C, iProlastin-C ifundwe kwizifundo ezingama-62 kwizifundo ezi-2 ezahlukeneyo zeklinikhi. Isifundo sokuqala yayisifundo se-crossover pharmacokinetic.[Bona Ikhemesti yezonyango (12.3) ]Ityala lesibini le-Prolastin-C lalingumbindi weziko elinamacandelo amaninzi, isifundo sokhuseleko lwengalo enye esivulelweyo ukuvavanya ukhuseleko kunye nokunyamezeleka kweProlastin-C. Kolu phononongo, izifundo ze-38 zaphathwa nge-infravenous infusions ye-60 mg / kg ubunzima bomzimba weProlastin-C kangangeeveki ezingama-20. Isiqingatha sezifundo zazingafakwanga kwiAlfa yangaphambili1Ukongezwa kwe-PI ngaphambi kokungena kufundo kwaye esinye isiqingatha sasifumana ukongezwa ngePROLASTIN ngaphambi kokungena kufundo. Ukuchongwa kweAlfa ebukhali1Ukusilela kwe-PI kwaqinisekiswa ngumboniso wohlobo lwePiZZ kwi-32 yama-38 (i-84.2%) yezifundo, kunye ne-6 ye-38 (15.8%) yezifundo ezithiwe thaca ezinye i-alleles ezaziwayo ukuba zikhokelela kwi-Alpha1Ukusilela -PI. La maqela ahanjiswa ngokulinganayo phakathi kwe-naïve kunye ne-non-naïve cohorts.

IZALATHISO

  1. Umbutho waseMelika weTroac; Umbutho Wokuphefumla waseYurophu. I-American Thoracic Society / i-European Respiratory Society statement: imigangatho yokuchongwa kunye nolawulo lwabantu abane-alpha-1 antitrypsin defence. NdinguJ J wokuKhathalela uKhathalelo ngeMed Med. Ngo-2003; 168: 818-900.

  2. UMolloy K, uHersh CP, uMorris VB, et al. Ukucaciswa komngcipheko wesifo esinganyangekiyo semiphunga kwi-α1-antitrypsin defence PiMZ heterozygotes. NdinguJ J wokuKhathalela uKhathalelo ngeMed Med. Ngo-2014; 7: 419-27.

  3. ICrystal RG. Ukuswela i-α1-Antitrypsin, i-emphysema, kunye nesifo sesibindi; isiseko semfuza kunye nezicwangciso zonyango. J Eklinikhi yokuTyala. Ngo-1990; 85: 1343-52.

  4. I-World Health Organization. Ukusilela kwe-Alpha-1-antitrypsin: Imemorandam evela kwintlanganiso ye-WHO. Inkunzi yezeMpilo kwiHlabathi liphela. Ngo-1997; 75: 397-415.

  5. I-Turino GM, iBarker AF, i-Melythisi ML, uCohen AB, uConnelly RP, uCrystal RG, et al. Iimpawu zeklinikhi zabantu abathile abane-PI * SZ phenotype yokusilela kwe-α1-antitrypsin. NdinguJ J wokuKhathalela uKhathalelo ngeMed Med. Ngo-1996; 154: 1718-25.

  6. Umbutho waseAmerican Thoracic. Izikhokelo zendlela yokusondela kwisigulana esine-alpha-1-antitrypsin. Ngaba ngu-Rev Respir Dis. Ngo-1989; 140: 1494-7.

  7. Wewers MD, Casolaro MA, Abathengisi SE, Swayze SC, McPhaul KM, Wittes JT, et al. Unyango olulandelayo lwe-alpha1Ukusilela kwe-antitrypsin okunxulunyaniswa ne-emphysema. N Eng J Med. Ngowe-1987; 316: 1055-62.

Unikezo / ugcino kunye nokusingathwa

  • Iprolastin-C LIQUID ibonelelwa ngeebhotile zedosi enye kunye neAlfa iyonke1Umsebenzi osebenzayo wePI, kwii-milligram, ezichazwe kwileyibhile yebhotile kunye nebhokisi.
  • Izinto zokupakisha azinayo i-latex yendalo yerabha.
NDC ibhokisi Ibhokisi le-NDC Uqikelelo lweAlfa1–PI
Umsebenzi wokuSebenza
Umthamo
13533-705-31
13533-705-01
13533-705-51
13533-705-32
13533-705-11
13533-705-52
500 mg
I-1,000 mg
4,000 mg
I-10 ml
20 ml
I-80 mL
  • Gcina ifriji kwi-2-8 ° C (36-46 ° F) ixesha eliboniswe ngumhla wokuphelelwa kwelebheli.
    • Imveliso inokugcinwa kubushushu bamagumbi obungagqithiyo kuma-25okanyeC (77okanyeF) ukuya kuthi ga kwinyanga enye, emva koko imveliso kufuneka isetyenziswe okanye ilahlwe kwangoko.
  • Musa ukubanda.
  • Lahla isahlulo esingasetyenziswanga.

Ulwazi ngeNgcebiso ngezigulana

  • Yazisa abaguli ngemiqondiso yokusabela hypersensitivity kubandakanya pruritus; urticaria ngokubanzi; ukugungxula; Ukudumba imilebe, ulwimi, okanye uvule; ukuvutha; ukuqina kwesifuba; idyspnea; uxinzelelo lwegazi; kunye ne syncope. Cebisa abaguli ukuba bayeke ukusetyenziswa kwemveliso kwaye banxibelelane nogqirha wabo kunye / okanye bafune ukhathalelo olukhawulezileyo, kuxhomekeke kubukhali bempendulo, ukuba ezi mpawu zenzeka.[Bona Izilumkiso kunye noKhuseleko (5.1) ]
  • Yazisa abaguli ukuba iProlastin-C LIQUID yenziwe ngeplasma yomntu kwaye inokuba semngciphekweni wokuhambisa ii-arhente ezosulelayo ezinokubangela izifo (umz. Chaza ukuba umngcipheko wokuba iProlastin-C LIQUID idlulise into echaphazelayo iye yehliswa ngokuthi kuhlolwe abo banikela ngeplasma ukuze babhencwe kwangaphambili zizinto ezithile ezosulelayo, ngokuvavanya iplasma enikelweyo kusulelo oluthile lwentsholongwane, nangokungasebenzi kunye / okanye nokususa iiarhente ezosulelayo ngexesha lokuvelisa. .[Bona Izilumkiso kunye nokuQapha (5.2) ]
  • Yazisa abaguli ukuba ulawulo lweProlastin-C LIQUID lubonakalisiwe ukuphakamisa inqanaba leplasma yeAlfa1-PI, kodwa ukuba isiphumo solonyuselo kwi-pulmonary exacerbations nakwinqanaba lokuqhubela phambili kwe-emphysema aliboniswanga kumandla olawulo olwaneleyo, olungenamkhethe, nolulawulwayo kuyo nayiphi na iAlfa1-PI imveliso.[Bona Izifundo zeKlinikhi (14) ]

Yenziwe ngu:

IGrifols Therapeutics LLC
Uphando lwe-Triangle Park, NC 27709 USA

IU.S. Ilayisensi engu-1871
3058807/3059108

ILEBHILE YEPHEPHA

I-NDC 13533-705-01

20 ml

UAlfa1-Iproteinase Inhibitor (yoLuntu)

IPROLASTIN®C
ULwelo

Isisombululo senaliti

Ukuphathwa kwe-detergent ye-solvent
Ifunyenwe

Rx kuphela

UKUKHULA

Isigulana nogqirha kufuneka baxoxe ngomngcipheko kunye nezibonelelo zale mveliso.

Isisombululo kunye nolawulo:
Funda okufakelweyo kwiphakheji.

Gcina ifriji kwi-2 ukuya kwi-8 ° C (36 ukuya kwi-46 ° F) ngaphandle kwenyanga e-1 kubushushu bamagumbi (ukuya kuthi ga kuma-25 ° C; 77 ° F) emva koko imveliso kufuneka isetyenziswe okanye ilahlwe kwangoko. Sukuyisebenzisa emva komhla wokuphelelwa kwayo.
Musa ukubanda.

UMTHAMO:
Ibhotile enye yeProlastin®-C Ulwelo

Akukho kugcina

Ulawulo efakwa kuphela

Oyinyumba-nonpyrogenic

IU.S. Ilayisensi engu-1871

LE MVELISO ILUNGISWE KWIIMBHOKO EZINKULU ZEEPASMA ZABANTU EZINOKUQUKETHA ABAHLOBO ABANGASETYENZISWAYO.

BONA IZILUMKISO ZOKUFAKA IPHEPHA.

Ibhotile yedosi enye
Sukusebenzisa if i-turbid.
Lahla isahlulo esingasetyenziswanga.
Musa ukugcina emva kokungena kwi-vial.
Lawula kwisithuba seeyure ezi-3 emva kokulungiswa.

I-1 mL iqulethe malunga ne-50 mg Alpha1-Iproteinase Inhibitor (yoLuntu),
2.76 mg ye-sodium phosphate,
22.27 mg L-alanine, kunye namanzi.

Ukuba ibhendi yokuncipha ayikho okanye ibonisa naluphi na uphawu lokuthintela, ungasebenzisi imveliso kwaye wazise iGrifols Therapeutics LLC kwangoko.

Izinto zokupakisha azinayo i-latex yendalo yendalo

IGrifols Therapeutics LLC
Uphando lwePar Triangle, NC
Ngowama-27709 e-USA

Ibhokisi: 3058831

ILOTI XXXXXXXXXX
I-EXP DDMMMYYYY
UMG A1-P1 XXXX
SN 4001XXXXXXXXXXX

IGTIN 00313533705015

I-NDC 13533-705-11

UAlfa1-Iproteinase Inhibitor (yoLuntu)

IPROLASTIN®C UTYWALA

ISISOMBULULO SOKUTOFA

Ukuphathwa kwe-detergent ye-solvent
Ifunyenwe

Isigulana nogqirha kufuneka baxoxe ngomngcipheko kunye nezibonelelo zale mveliso.

Akukho kugcina

Ulawulo efakwa kuphela

Oyinyumba-nonpyrogenic

Rx kuphela

20 ml

Isisombululo kunye nolawulo: Funda okufakwe ngaphakathi kwiphakheji.

Gcina ngo-2 ukuya ku-8 ° C (36 ukuya ku-46 ° F) kungabikho ngaphezulu kwenyanga enye kumaqondo obushushu egumbi (ukuya kuthi ga kuma-25 ° C; 77 ° F), emva koko imveliso kufuneka isetyenziswe okanye ilahlwe kwangoko.
Sukuyisebenzisa emva komhla wokuphelelwa kwayo.
Musa ukubanda.

IGrifols Therapeutics LLC
Uphando lwe-Triangle Park, NC 27709 USA
IU.S. Ilayisensi engu-1871

3058828

Lot / Ex. / mg a1-PI

IProlastin-C LIQUID
Ialpha1-proteinase inhibitor (yabantu) inaliti, isisombululo
Ulwazi lweMveliso
Uhlobo lweMveliso UKUQHUTYELWA KWE-PLASMA Ikhowudi yento (Umthombo) I-NDC: 13533-705
Umgaqo woLawulo EZIQHELEKILEYO Ishedyuli ye-DEA
Isithako esisebenzayo / Umoya oSebenzayo
Igama lezithako Isiseko soMandla Amandla
.alpha.1-proteinase Inhibitor yoLuntu (. alpha.1-proteinase Inhibitor yoLuntu) .alpha.1-proteinase Inhibitor yoLuntu I-1000 mg kwi-20 mL
Izithako ezingasebenziyo
Igama lezithako Amandla
Isodium Phosphate
UAlanine
Amanzi
Iimpawu zeMveliso
Umbala IMFUYO (ecacileyo, engenambala okanye emthubi okanye emthubi eluhlaza) Inqaku
Imilo Ubungakanani
Incasa Ikhowudi yoShicilelo
Iqulathe
Ukupakisha
# Ikhowudi yento Inkcazo yephakheji
1 I-NDC: 13533-705-01 I-1 VIAL KWI-1 CARTON
1 I-NDC: 13533-705-11 I-20 mL kwi-1 VIAL
2 I-NDC: 13533-705-31 I-1 VIAL KWI-1 CARTON
2 I-NDC: 13533-705-32 10 ml kwi-1 VIAL
3 I-NDC: 13533-705-51 I-1 VIAL KWI-1 CARTON
3 I-NDC: 13533-705-52 I-80 mL kwi-1 VIAL
Ulwazi lweNtengiso
Udidi lokuThengisa Inombolo yesicelo okanye iMonograph Citation Umhla wokuQalisa ukuThengisa Umhla Wokuphela Wentengiso
LUHLAZA BLA103174 02/12/1987
Umlebheli -IGRIFOLS USA, LLC (048987452)
Ukusekwa
Igama Idilesi I-ID / FEI Imisebenzi
IGrifols Therapeutics LLC 611019113 ukuvelisa (13533-705)
Ukusekwa
Igama Idilesi I-ID / FEI Imisebenzi
IZiko leGrifols SA 465562213 ukuvelisa (13533-705)
Ukusekwa
Igama Idilesi I-ID / FEI Imisebenzi
I-GRIFOLS KWIMISEBENZI YONKE YONYAKA EYENZIWEYO Yimi ileyibhile (13533-705), ipakethi (13533-705)
IGRIFOLS USA, LLC

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