ibrutinib

imbruvikka enna brand naamatthil vilkkunna ibrutinib, brutoninte tyrosine kinez (bii. tii. keey) proteine maattaanaavaatha reethiyil bandhippikkunnathiloode bii-sell vyaapanatheyum athijeevanatheyum thadayunna oru cheria thanmatra marunnaan. bii-sell risapttar paathaye bii. tii. keey thadayunnathu thadayunnu, ithu bii sell kaansarukalil palappozhum asaadhaaranamaayi sajeevamaan. athinaal maandil sell lymphoma, chronic lymphocytic leukemia, waldenstroms macroglobulinemia ennivayulppedeyulla arbudangal chikilsikkaan ibrutinib upayogikkunnu. sii-terminal src kainasukalumaayum ibrutinib bandhippikkunnu. iva bii. tii. keey inhibittarinte oof-taargett resepterukalaanu. ibrutinib eee resepterukalumaayi bandhippikkukayum koshangalude vyathyasavum valarchayum prothsaahippikkunnathil ninnu kainesine thadayukayum cheiyunnu. vittumaaraatha lymphocytic leukemiyayude chikilsaykkide idathu atrial valippam, atrial fibrilation thudangi niravadhi paarshwafalangalilekku ithu nayikkunnu.
lokaarogya samghadanayude avashya marunnukalude pattikayil ithu ulppedunnu.
medical upayogangal.
maandil sell lymphoma (mcl), chronic lymphocytic leukemia (cll)/small lymphocytic lymphoma (sll), waldenstroms macroglobulinemia (doubleum), marginal soonn lymphoma (emsl), chronic graaft vezhsas hoost disease (cgvhd) ennivayude chikilsaykkaayi ibrutinib soochippikkunnu.
prathikoola phalangal.
pneumonia, upper respiratory tract anubadha, sinasitis, charmma anubadha, neutrophil ennam kurayuka, platelettukalude ennam kurayuka, thalavedana, rakthasraavamundaakuka, murivu, vayarilakkam, chharddi, vaayilum chundilum veekkam, ookkaanam, malabandham, paadukal, sandhi vedana, peshivedana, musculoskelital vedana, panii, edema enniva valare saadhaaranamaaya (10 sathamaanam aavruthi) prathikoola phalangalil ulppedunnu.
sepsis, moothranaaliyile anubadha, melanoma ithara charmma arbudam (basel-sell carcinoma, schwamous sell carcinoma), kuranja leukosite kaundu, kuranja lymphosite kaundu, intersteeshyal shwaasakosha rogam, tumour lysis syndrome, uyarnna euric assid alavu, thalakarakkam, mangiya kazhcha, atrial fibrilation, subdural hematoma, mookkil ninnu raktham varunnath, takarnna rakthakkuzhalukalil ninnulla cheria murivukal, uyarnna rakthasammardham, theneechakkoodukal, charmmatthil chuvapp allengil blushing enniva saadhaarana (1-10% aavruthi) prathikoola phalangalil ulppedunnu.
farmacology.
ibrutinib ooral bioavilability upavaasaavasthayil 3.9 sathamaanavum, bhakshanam nalkunna avasthayil 8.4 sathamaanavum, munthirippazham jyoos kazhichathinu sesham 15.9% aanu.
samvidaanam.
brutoninte tyrosine kainesinte (bii. tii. keey) shakthavum thirichedukkaanaavaathumaathu inhibittaraanu ibrutinib. ithu bii. tii. keey. active saittile sisttain avashishtamaaya avashishtamaaya oru kovalant boond roopappeduthunnu, ithu bii. tii. keey. ensaimatik pravartthanatthe susthiramaayi thadayunnathilekku nayikkunnu. maanttil sell lymphoma (emm. sii. ell), defuse large bii-sell lymphoma (dii. ell. bii. sii. ell), follicular lymphoma, chronic lymphocytic leukemia (sii. ell. ell) ennivayulppede niravadhi bii-sell maarakathvangalude rogakaarikalil punk vahikkunna bii-sell aantijan risapttar (bii. sii. aarr) paathayile oru pradhana signalling thanmathrayaanu bii. tii. keey. preclinical padanangal kaanikkunnath ibrutinib marakamaaya bii-sell vyaapanatheyum vivoyile athijeevanatheyum athupole thanne sell migration substrate addition inn vitroy phalapradamaayi thadayunnu ennaanu.
aadyakaala klinikkal padanangalil, ibroottinibinte pravartthanatthil lymphodenopathy vegathil kurayunnathum shanikamaaya lymphocytosis ulppedunnu, ithu koshangalude homingilo tissue microenvionmentile gadakangalilekkulla kudiyettatthilo marunnu nerittu swaadheenam cheluthiyekkaamennu soochippikkunnu.
vittumaaraatha lymphocytic leukemia (cll) koshangalekkurichulla preclinical padanangalil, ibrutinib apoptosis prolsaahippikkumennum vyaapanathe thadayumennum microenvionment nalkunna athijeevana uthejakangalodu prathikarikkunnathil ninnu cll koshangale thadayumennum report cheyyappettittund. ithu marakamaaya bii koshangalile koshangalile alavu (aanti-apoptotic protein) kuraykkunnathilekkum nayikkunnu. ibrutinib upayogichu sajeevamaaya cll koshangalude chikitsa bii. tii. keey tyrosine phosphorylation thadayunnathinum erk 1/2, 1/2, enf-kebi ennivayulppede eee kinace sajeevamakkiya thaazhekkulla athijeevana pathakal phalapradamaayi raddaakkunnathinum kaaranamaayi. koodaathe, ibrutinib vitrokalile sii. ell. ell koshangalude vyaapanathe thadayukayum layikkunna gadakangal (baff, ail-6, ail-4, tii. enn. eph-α), fibronectin edapedal, stromal sell kondaakt ennivayulppede microenvionmentil ninnulla sii. ell. ell koshangalkk baahyamaayi nalkunna athijeevana signalukale phalapradamaayi thadayukayum cheythu.
ibrutinib keemokkainukalaaya cxcl 12, cxcl 13 ennivayilekkulla vittumaaraatha lymphocytic leukemia sell chemotaxis kuraykkumennum bii-sell resepterile (bcr) uthejanathethudarnnu sellular additione thadayumennum report cheyyappettittund. koodaathe, cxcr4/sdf1 axis targettucheythu cd20 (retuximab/ofattumumaabinte taargett) yude expression ibrutinib daun-modulate cheiyunnu.
eee daatta orumichu, ibrutinib bii. sii. aarr signalingine thadayunna oru mechanical modalumaayi poruthappedunnu, ithu koshangale apoptosisilekku nayikkukayum koodaathe/allengil koshangalude kudiyettattheyum samrakshana tumour microenvayonmentukale anusaranatheyum thadassappeduthunnu.
charithram.
bii. tii. keey pravartthanam padikkunnathinulla oru upakarana samyukthamaayi selera genomicsile shaasthranjaraanu ibrutinib srishtichathu; ithu oru riyejantinu anuyojyamaayathum ennaal pothuve marunnukalkk anuyojyamallaathathumaya athinte lakshyathe sahavarthithvathode bandhippikkunnu.
2006-ll, swantham prarambha kandethal paripadi paraajayappettathin sesham celerayil ninnu oru echu. dii. eiii. sii-kendreekritha prograam nedunnathinidayil, pharmacyclics seleerayude cheria thanmatra bii. tii. keey inhibittar discovery prograam 2 milyan dollar panatthinum 1 milyan dollar stokkinum eduthu tool komboundinu pii. sii. aii-32765 ennu perittu. 2011-ll marunnu randaam ghatta pareekshanangal poortthiyaakkiya sesham, jonson & jonson, pharmacysics ennivar marunnu saha-vikasippikkaan sammathichu, jeey & jeey pharmacysic 150 milyan dollar 825 milyan dollar munkootty nalki. 2015 meyy maasathil faarmasisiklikkukal abvi ettedukkukayum 2016ll oru bilyan dollar 2020ll 5 bilyan dollar aagola vilppana nadathumennu abvi pravachikkukayum cheythu.
2013 novemberil yuu. ezz phudu aandu drugg administration (eph. dii. eiii) maanttil sell lymphomayude chikilsaykkaayi ithinu amgeekaaram nalki. 2014 februvariyil, fda ibroottinibinte amgeekritha upayogam vittumaaraatha lymphocytic leukemia (cll) lake vipuleekarichu. 2015ll waldenstrom macroglobulinemiac ithu amgeekarichu.
2015 maarchil, farmacislix abviyum 21 bilyan dollarinu faarmasisliksukal vaangumenn sammathichu; karar poortthiyaayi.
2016 maarchil, vittumaaraatha lymphocytic leukemia (cll) ulla rogikalkkaayi amerikkayil ibroottinibinte oru puthiya soochana amgeekarichu.
2016 meyy maasathil, vittumaaraatha lymphocytic leukemia (cll), cheria lymphocytic lymphoma (sll) ennivaykku amerikkayil ibroottinibinte oru puthiya soochana amgeekarichu.
2017 januvariyil, systemic therapy aavasyamullathum kuranjathu oru munkaala munkaala adisthaanamaakkiyulla theraappiyenkilum labhichathumaaya relapsed/refractory (aarr/aarr) marginal soonn lymphoma (emsl) ulla muthirnnavarude chikilsaykkaayi amerikkayil ibrutinibinu oru puthiya soochana amgeekarichu.
2017 augustil, graaft-vezhsas-hoost rogathe chikilsikkunnathinaayi ibruttinibinu oru puthiya soochanaykku fda amgeekaaram nalki. eee avasthaykku eph. dii. eiii amgeekaricha aadyathe marunnaanith.
2018 februvariyil, amerikkayil upayogathinaayi ibroodinibinte oru gulika roopeekaranathinu amgeekaaram labhichu.
2018 augustil, retuximabinoppam ibrutinib amerikkayil waldenstroms macroglobulinemia (doubleum) ulla muthirnnavarude chikilsaykkaayi amgeekarichu, ithu apoorvavum chikilsikkaan kazhiyathathumaaya tharam hodkins lymphomayanu (enll).
munbu chikilsikkaattha vittumaaraatha lymphocytic leukemia/small lymphocytic lymphoma (sii. ell. ell/ezz. ell. ell) ulla muthirnnavarude chikilsaykkaayi 2019 januvariyil obinyoottusumabumaayi samyojippichu ibrutinib amgeekarichu.
2020 eprilil, vittumaaraatha lymphocytic leukemia (cll) allengil cheria lymphocytic lymphoma (sll) ulla muthirnnavarude prarambha chikilsaykkaayi retuximabumaayi samyojippichu ibrudinibinte soochana fda vipuleekarichu. iii1912 trial (enn. tii. tii. 02048813), 2:1 kramarahithamaya, multisenter, ooppan-label, retuximab upayogichu ibroottinibinte sajeevamaayi niyantritha trial ennivaye adisthaanamaakkiyullathaanu amgeekaaram, 70 vayaso athil thaazheyo praayamulla 529 muthirnnavaril fluiderabin, cyclophosphamide, retuximab (eph. sii. aarr) ennivayumaayi thaarathamyappeduthumbol munbu chikilsikkaattha sii. ell. ell allengil ezz. ell. ell systemic therapy aavasyamaanu.
samoohavum samskaaravum.
saambathikashaasthram.
jansen farmaceutica pharmacysics 2018-nte aadya pakuthiyil oru phlait prising gadanayulla oru puthiya single doses tablet formulation avatharippikkukayum capsule formulation nirthalaakkukayum cheythu. ithu sharashari rogiyude vilayil moonnirattiyaakkumennu karuthiyathinaal ithu prathishedhatthinu kaaranamaayi.
nilavil capsule, tablet roopangalil labhyamaya marunnu upayogichu capsule formulation nirthaanulla theerumaanam jansen farmaceutica farmacislix pinvalichu.
2018ll australian farmaceutical benefits schemil ibrutinib chertthu.
2020ll indian farmaceutical aanukoolya padhathiyil generic ibrutinib chertthu.

