Mndandanda wa mankhwala a insulin degludec * (insulin degludec *)

Jekeseni 100 U / ml

1 ml yankho lili

ntchito yogwira - insulin degludec * - 100 PIECES (3.66 mg),

obwera: phenol, metacresol, glycerol, zinc, hydrochloric acid / sodium hydroxide (kukonza pH), madzi a jekeseni.

* yopangidwa ndi recombinant DNA biotechnology pogwiritsa ntchito mavuto Saccharomycesachina

Makatoni amodzi amakhala ndi 3 ml ya yankho, lofanana ndi 300 PIERES.

Transparent colorless solution.

Mankhwala

Pharmacokinetics

Pambuyo pa jekeseni wa subcutaneous, kupanga mapangidwe osungunuka a insulin degludec multhexamers, omwe amapanga insulin depot mu subcutaneous adipose minofu. Multihexamers pang'onopang'ono amadzisiyanitsa, ndikumasokoneza maukodifine a insludec, zomwe zimapangitsa kuti magazi azilowa pang'onopang'ono m'magazi.

Kuchulukitsa kwa Tresiba® mu plasma kumachitika pambuyo pa masiku awiri ndi atatu a tsiku lililonse.

Kuchita kwa insulin degludec kwa maola 24 ndi kayendetsedwe kake ka tsiku lililonse kamodzi patsiku kumagawidwa chimodzimodzi pakati pa nthawi yoyamba ndi yachiwiri ya maola 12 (AUCGIR, 0-12h, SS / AUCGIR, vene, SS = 0.5).

Kuyanjana kwa insludec insulin ya serum albin kumafanana ndi kuchuluka kwa mapuloteni a plasma> 99% m'madzi am'magazi a anthu.

Chotsogola

Ndi subcutaneous makonzedwe, onse plasma wozungulira anali mogwirizana ndi mlingo kutumikiridwa mu osiyanasiyana achire Mlingo.

Magulu apadera a odwala

Odwala okalamba, odwala mafuko osiyanasiyana, odwala amuna kapena akazi osiyana siyana, odwala omwe ali ndi vuto laimpso kapena chiwindi

Panalibe kusiyana kwakukulu pama pharmacokinetics a Tresiba Penfill® pakati pa odwala okalamba ndi achinyamata, pakati pa odwala amitundu yosiyanasiyana, pakati pa odwala omwe ali ndi vuto la impso kapena chiwindi ndi odwala athanzi.

Panalibe kusiyana mu mankhwala a pharmacokinetic a mankhwalawa kutengera mtundu wa wodwalayo.

Ana ndi achinyamata

Mankhwala a Tresiba Penfill ® mu kafukufuku wa ana (1 mpaka 11) ndi achinyamata (wazaka 12-18) wokhala ndi mtundu woyamba wa matenda a shuga ndi ofanana ndi omwe ali ndi odwala akulu omwe ali ndi jakisoni imodzi.

Zotsatira zonse za kuchuluka kwa insuludec insulin mwa ana ndi achinyamata ndiwokwera poyerekeza ndi odwala omwe ali ndi vuto limodzi la mankhwala kwa odwala omwe ali ndi matenda ashuga 1.

Mankhwala

Tresiba® Penfill ® ndi chithunzi cha insulin yaanthu yomwe imakhala nthawi yayitali yopangidwa ndi recombinant DNA biotechnology pogwiritsa ntchito Saccharomyces cerevisiae strain.

Tciousba® Penfill ® ndi mndandanda wofunikira wa insulin ya anthu omwe akhala akuchita kwakanthawi. Pambuyo pa jekeseni wa subcutaneous, gawo loyambira la mankhwala (insulin degludec) limasungunuka kosakanikirana kosiyanasiyana mu deputeraneous depot, komwe kumakhala kupitiliza pang'onopang'ono kwa insulin degludec kuzungulira, ndikuwonetsa pang'onopang'ono zochitika ndi kukhazikika kwa hypoglycemic.

Munthawi ya kuwunika kwa maola 24 a hypoglycemic zotsatira za mankhwala kwa odwala omwe mankhwalawa a degludec insulin adalandira kamodzi patsiku, mankhwala a Tresiba Penfill ®, mosiyana ndi insulin glargine, adawonetsa kuchuluka kwa magawidwe pakati pa zomwe zinachitika nthawi yoyamba ndi yachiwiri ya maola 12. (AUCGIR, 0-12h, SS / AUCGIR, chonse, SS = 0.5)

Mkuyu. 1. Maola 24 a maola ambiri kulowetsedwa kwa glucose infrudec - equilibrium degludec insulin ndende ya 100 PIECES / ml 0,6 PIECES / kg (kafukufuku wa 1987)

Kutalika kwa mankhwalawa Tresiba Penfill® ndi maola opitilira 42 kuchokera munthawi ya achire. Kufanana kwa mankhwalawa kwa magazi m'madzi am'magazi kumatheka patatha masiku 2-3 atatha kugwiritsa ntchito mankhwalawa.

Insulin degludec mu equilibrium ndende ikuwonetsa kuchepa kwambiri (maulendo 4) poyerekeza ndi insulin glargin tsiku lililonse kusinthasintha kwa hypoglycemic kanthu, komwe kamayesedwa ndi phindu la kuchuluka kwa kusiyanasiyana (CV) pophunzira zotsatira za hypoglycemic ya mankhwala pakadutsa kamodzi mpaka maola 24 mpaka 24 ( AUCGIR, ed, SS) komanso mkati mwa nthawi kuchokera 2 mpaka maola 24 (AUCGIR, 2-24h, SS) (Table 1).

Tab. 1. Kusintha kwa kusintha kwatsiku ndi tsiku kwa zotsatira za hypoglycemic ya mankhwala a Tresiba ndi insulin glargine mu gawo lofanana mwa odwala omwe ali ndi matenda a shuga 1.

Kusintha kwamasamba tsiku ndi tsiku a hypoglycemic nthawi imodzi dosing (AUCGIR, vene, SS)

Kusintha kwamasamba a tsiku lililonse a hypoglycemic nthawi ya pakati 2 mpaka 24 maola (AUCGIR, 2-24 h, SS)

CV: cholowa chimodzi

SS: kugwiritsa ntchito mankhwala osokoneza bongo molingana

AUCGIR, 2-24h: metabolic zotsatira mu maola 22 otsiriza a dosing interval (i.e., palibe mphamvu pa izo ya kulowetsedwa kwa insulin panthawi yophunzira koyambira).

Ubwenzi wapakati pa kuwonjezeka kwa mlingo wa Tresiba Penfill® ndi zotsatira zake zazikulu za hypoglycemic zatsimikiziridwa.

Maphunzirowa sanawonetse kusiyana kwakukulu mu pharmacodynamics ya mankhwala a Tresiba pakati pa odwala okalamba ndi odwala achinyamata.

Kuchita Mwachipatala ndi Chitetezo

Miyezi 11 yapadziko lonse lapansi yoyesedwa mosakayikira idachitika mu regimen "Therapy to the target" wokhala ndi milungu 26 ndi 52, wopangidwa m'magulu awiriwa, omwe anaphatikiza odwala 4275 omwe ali ndi matenda a shuga a mellitus (1102 odwala matenda ashuga 1 ndi odwala 3173 omwe ali ndi matenda a shuga mtundu wa 2 matenda ashuga) wochiritsidwa ndi Tresiba®.

Kuchita bwino kwa Tresiba® kunaphunziridwa mwa odwala omwe ali ndi vuto la matenda a shuga 1 (Table 3), mwa odwala matenda a shuga 2 omwe sanalandire insulin kale (kukhazikitsidwa kwa mankhwala a insulin, Table 4), ndi omwe adalandira insulin Therapy ) munthawi yomweyo mankhwala a Tresiba® (Table 6).

Kusakhalapo kokulirapo kwa mankhwala oyerekeza (insulin detemir ndi insulin glargine) pa mankhwala a Tresiba® pokhudzana ndi kuchepa kwa glycated hemoglobin (HbA1c) kuyambira panthawi yophatikizira kumapeto kwa kafukufukuyu. Chosiyana ndi ichi chinali mankhwala a sitagliptin, poyerekeza ndi momwe mankhwalawa Tresiba® adawonetsera kukula kwake mokhudzana ndi kuchepa kwa HbA1c (Table 5).

Zotsatira zakufufuza kwakanthawi kwa zovuta zomwe zapezeka m'mayeso 7 azachipatala omwe anakonzedwa pamaziko a "Chithandizo mpaka cholinga" ndi kutenga nawo mbali kwa odwala omwe ali ndi mtundu woyamba wa 2 ndi mtundu wa matenda ashuga 2 adawonetsa maubwino a chithandizo cha Tresiba pankhani yotsika poyerekeza ndi mankhwala a insulin glargine , pafupipafupi chitukuko cha odwala omwe ali ndi ma episode a nocturnal hypoglycemia (Gome 2). Kuchepetsa kwa kuchuluka kwa hypoglycemia panthawi ya mankhwala a Tresib ® kunatheka chifukwa cha kutsika kwa glucose wotsika kwambiri kuposa insulin glargine.

Tebulo 2. Kusanthula kwa deta ya gawo hypoglycemia

Magawo pkuvomerezaennoyhypoglycemiandikoma

Kuyerekeza Kuwopsa Kwamavuto

(insulin degludec / insulin glargine)

Zonse

Usikus

Mtundu woyamba wa matenda ashuga 1 mtundu wa shuga 2

Kufotokozera za mankhwalawa

Insulin degludec * (Insulin degludec *) - Mankhwala Insulin degludec * (Insulin degludec *) ® Penfill ® - insulin yopanga anthu kwa nthawi yayitali yopangidwa ndi recombinant DNA biotechnology yogwiritsa ntchito Saccharomyces cerevisiae strain.

Insulin degludec imamangiriza makamaka ku cholandilira cha insulin ya insulin ya anthu ndipo, ikulumikizana nayo, imazindikira mphamvu yake ya pharmacological yofanana ndi mphamvu ya insulin yaumunthu.

Mphamvu ya hypoglycemic ya degludec insulin imayamba chifukwa cha kugwiritsidwa ntchito kwa glucose pogwiritsa ntchito minofu pambuyo pomangiriza insulin kutikita minofu ndi ma cell cell receptors komanso kuchepa kwa munthawi yomweyo.

The Tresiba Penfill ® ndi chiyambi choyambirira cha insulin yaumunthu yopitilira muyeso, atatha kupaka jakisoni wamkati amapanga kusungunuka kosiyanasiyana kosungirako, komwe kumakhala kuyamwa kosalekeza kwa insludec m'mitsempha yamagazi, komwe kumapereka chidziwitso chambiri komanso chokhazikika cha mankhwala. Munthawi ya kuwunika kwa maola 24 a hypoglycemic zotsatira za mankhwala kwa odwala omwe mankhwalawa a degludec insulin adalandira kamodzi patsiku, mankhwala a Tresiba Penfill®, mosiyana ndi insulin glargine, adawonetsa kuchuluka kwa magawidwe pakati pazomwe zinachitika panthawi yoyamba komanso yachiwiri ya maola 12 ( Auc_{GiR, 0-12h, SS}/ Auc_{GiR, yathunthu, SS} = 0.5).

Kutalika kwa mankhwalawa Tresiba Penfill® ndi maola opitilira 42 kuchokera munthawi ya achire. Kufanana kwa mankhwalawa kwa magazi m'madzi am'magazi kumatheka patatha masiku 2-3 atatha kugwiritsa ntchito mankhwalawa.

Insulin degludec mu equilibrium ndende ikuwonetsa kuchepa kwambiri (maulendo 4) poyerekeza ndi insulin glargin tsiku lililonse kusinthasintha kwa hypoglycemic kanthu, komwe kamayesedwa ndi phindu la kuchuluka kwa kusiyanasiyana (CV) pophunzira zotsatira za hypoglycemic ya mankhwala munthawi imodzi ya dosing._{GiR, t, SS}) komanso mkati mwa nthawi yopitilira maola 2 mpaka 24 (AUC_{GiR, 2-24h, SS}), onani Gawo 1.

Gome 1. Kusintha kwa mitundu ya tsiku ndi tsiku ya hypoglycemic ya mankhwala a Tresiba ndi insulin glargine ali m'malo azofanana odwala omwe ali ndi vuto la matenda a shuga 1.

CV ndiye mgwirizano wosinthasintha wapakati pa%,

SS ndiyo kuchuluka kwa mankhwalawa munthawi yomweyo,

Auc_{GiR, 2-24h, SS} - kagayidwe kachakudya mu maola 22 omaliza a gawo la dosing (ndiye kuti, palibe zotsatira zake pa kulowetsedwa kwa insulin panthawi yoyambitsa kuphunzira kwa clamp).

Ubwenzi wapakati pa kuwonjezeka kwa mlingo wa Tresiba Penfill® ndi zotsatira zake zazikulu za hypoglycemic zatsimikiziridwa.

Maphunzirowa sanawonetse kusiyana kwakukulu mu pharmacodynamics ya mankhwala a Tresiba pakati pa odwala okalamba ndi odwala achinyamata.

Kuchita Mwachipatala ndi Chitetezo

Atachita mayeso 11 otseguka padziko lonse lapansi a test-to-Target (njira ya "kuchiritsa bwino") masabata 26 ndi 52, opangidwa m'magulu ofananirako, omwe anaphatikiza odwala 4275 (1102 odwala omwe ali ndi matenda ashuga 1 ndi 3173 woleza wodwala mtundu wachiwiri wa matenda a shuga (mellitus) omwe amathandizidwa ndi Tresiba®.

Kuchita bwino kwa Tresiba® kunaphunziridwa mwa odwala omwe ali ndi vuto la matenda ashuga a mtundu woyamba omwe sanalandire insulin kale, komanso ndi mtundu wa 2 wodwala matenda a shuga omwe analandila mankhwala a insulin, munthawi yonse ya Tresiba®. Kusowa kwa kuphatikiza kwa mankhwala oyerekeza (insulin detemir ndi insulin glargia) pa Tresiba® pokhudzana ndi kuchepa kwa index ya HbA kwatsimikiziridwa_1C kuyambira pomwe ndikuphatikizira kumapeto kwa kafukufukuyu. Kupatula kwake kunali sitagliptin, pomwe Tresiba ® adawonetsa ukulu wake pokweza HbA_1C.

Zotsatira za kafukufuku wazachipatala (njira "yothandizira cholinga") yoyambitsa matenda a insulin odwala omwe ali ndi matenda a shuga 2 amawonetsa kuchepa kwa 36% pazochitika zotsimikizira za nocturnal hypoglycemia (zomwe zimafotokozedwa ngati gawo la hypoglycemia lomwe limachitika pakati pa nthawi ya 6 ndi 6 koloko m'mawa kutsimikizira kuyeza plasma shuga ndende b0.84*0.68* Okalamba okalamba ≥ wazaka 65 zakubadwa0.820.65* Mtundu woyamba wa shuga1.10.83 Mlingo kukonzanso nthawi b1.020.75* Type 2 shuga0.83*0.68* Mlingo kukonzanso nthawi b0.75*0.62* Chithandizo chapansi chokha mwa odwala omwe sanalandire insulin0.83*0.64*

* Zambiri
a - g-yotsimikizika hypoglycemia ndi gawo la hypoglycemia, lomwe limatsimikiziridwa ndi muyeso wa plasma glucose concentration b - zochitika za hypoglycemia pambuyo pa sabata la 16 la mankhwala.

Panalibe kupangika kwofunikira kwambiri kwa ma antibodies ku insulin atalandira chithandizo ndi Tresiba Penfill® kwa nthawi yayitali.

Next Generation Insulin Yaitali

Kwa anthu odwala matenda ashuga, inshuwaransi ya anthu ya NPH komanso zochitika zake zazitali zomwe zilipo. Gome ili pansipa likuwonetsa kusiyana kwakukulu pakati pa mankhwalawa.

Mu Seputembara 2015, insulin yatsopano ya Abasaglar idayambitsidwa, yomwe ili yofanana ndi Lantus yubiquitous.

Wochedwa insulin

Food and Drug Administration (FDA, US FDA) - Bungwe la boma lomwe lachita pansi pa dipatimenti ya zaumoyo ku U.S. mu 2016 linavomerezanso mtundu wina wa insulin. Izi zimapezeka pamsika wapanyumba ndipo zimatsimikizira kuyenera kwake pochiza matenda ashuga.

NPH insulini (NPH Neutral Protamine Hagedorn)

Uwu ndi mtundu wa mankhwala a insulin opangira mapangidwe a insulin yaumunthu, koma olemeretsedwa ndi protamine (protein ya nsomba) kuti achepetse mphamvu yake. NPH ndi mitambo. Chifukwa chake, isanayambe makonzedwe, iyenera kuzunguliridwa bwino kusakaniza bwino.

NPH ndi mtundu wotsika mtengo kwambiri wa insulin. Tsoka ilo, imakhala ndi chiopsezo chachikulu cha hypoglycemia ndi kulemera kwakukulu, chifukwa imakhala ndi chiwonetsero chokwanira pantchito (ngakhale zimachitika pang'onopang'ono osati mwachangu ngati insulin pamabowo).

Odwala omwe ali ndi matenda amtundu woyamba 1 amapatsidwa kawiri kawiri la NPH insulin patsiku. Ndipo odwala omwe ali ndi matenda a shuga a 2 amatha jekeseni kamodzi patsiku. Zonse zimatengera kuchuluka kwa shuga m'magazi ndi malingaliro a dokotala.

Ma Anulin a Nthawi Yaitali a Insulin

Insulin, zomwe zimapangidwa ndi mankhwala omwe amasinthika kotero kuti amachedwetsa kuyamwa ndi mphamvu ya mankhwalawo, amadziwika kuti ndi insulin yopanga anthu.

Lantus, Abasaglar, Tujeo ndi Tresiba ali ndi zochitika zodziwika bwino - nthawi yayitali yogwirira ntchito komanso chiwonetsero chochepa kwambiri cha ntchito kuposa NPH. Mwanjira iyi, kudya kwawo kumachepetsa chiopsezo cha hypoglycemia ndi kulemera. Komabe, mtengo wa analogues ndiwokwera.

Abasaglar, Lantus, ndi Tresiba insulin amatengedwa kamodzi patsiku. Odwala ena amagwiritsanso ntchito Levemir kamodzi patsiku. Izi sizikugwira ntchito kwa odwala matenda ashuga 1 omwe mankhwalawa ndi ochepera maola 24.

Tresiba ndiye mtundu watsopano kwambiri ndipo tsopano ndi wotchipa kwambiri wa insulin pamsika. Komabe, ili ndi mwayi wofunikira - chiopsezo cha hypoglycemia, makamaka usiku, ndizotsika kwambiri.

Insulin imatenga nthawi yayitali bwanji

Udindo wa insulin yayitali ndikuwimira chinsinsi chachikulu cha insulini kudzera m'mapapo. Chifukwa chake, muyezo wofanana wa timadzi tomwe timagazi timatsimikizika pantchito yake yonse. Izi zimathandizira kuti maselo a thupi lathu agwiritse ntchito shuga wosungunuka m'magazi kwa maola 24.

Momwe mungabayitsire insulin

Ma insulini onse omwe akhala akuchita kwa nthawi yayitali amalowetsedwa pansi pa khungu m'malo omwe mumakhala mafuta. Gawo lotsatira la ntchafu ndilabwino kwambiri pazolinga izi. Malowa amalola kuti kulowetsedwa pang'onopang'ono komanso moyenera kwa mankhwalawo. Kutengera ndi nthawi ya endocrinologist, muyenera kuchita jakisoni imodzi kapena iwiri patsiku.

Kubayira pafupipafupi

Ngati cholinga chanu ndikusunga ma jakisoni a insulin ochepera momwe mungathere, gwiritsani ntchito Abasaglar, Lantus, Toujeo, kapena Tresiba analogues. Jakisoni m'modzi (m'mawa kapena madzulo, koma nthawi zonse nthawi yomweyo) amatha kupereka insulin yofananira ndi wotchi.

Mungafunike jekeseni awiri patsiku kuti mukhale ndi mahomoni azambiri zamagazi posankha NPH. Izi, zimakupatsirani kusintha kwa mankhwalawa kutengera nthawi yatsiku ndi zochitika - zapamwamba masana komanso zochepa pogona.

Chiwopsezo cha hypoglycemia pakugwiritsa ntchito insulin

Zatsimikiziridwa kuti ma insulin anime omwe amakhala nthawi yayitali amakhala osayambitsa hypoglycemia (makamaka hypoglycemia usiku) poyerekeza ndi NPH. Mukamagwiritsa ntchito, zofunika za glycated hemoglobin HbA1c ndizotheka.

Palinso umboni wosonyeza kuti kugwiritsa ntchito mankhwala okhala ndi insulin analoques nthawi yayitali poyerekeza ndi isoflan NPH kumayambitsa kuchepa kwa thupi (ndipo, chifukwa chake, kutsika kwa kukana kwa mankhwalawa komanso kufunika kwathunthu kwa mankhwalawo.

Kutenga nthawi yayitali insulin ya matenda a shuga a mtundu I

Ngati mukudwala matenda ashuga amtundu 1, kapamba wanu sangathe kupanga insulini yokwanira. Chifukwa chake, mutatha kudya chilichonse, muyenera kugwiritsa ntchito mankhwala omwe amathandizira kubisalira kwa insulin ndi maselo a beta. Ngati mwaphonya jakisoni, pamakhala chiopsezo chokhala ndi matenda ashuga a ketoacidosis.

Mukamasankha pakati pa Abasaglar, Lantus, Levemir ndi Tresiba, muyenera kudziwa zina mwazinthu za insulin.

• Lantus ndi Abasaglar ali ndi mbiri yosyasyalika pang'ono kuposa Levemir, ndipo kwa odwala ambiri, amagwira maola 24.
• Levemir angafunikire kutengedwa kawiri tsiku lililonse.
• Kugwiritsa ntchito Levemir, Mlingo umatha kuwerengeka malinga ndi nthawi ya tsiku, motero kuchepetsa chiopsezo cha nocturnal hypoglycemia ndikuwongolera kuwongolera kwa nthawi masana.
• Toujeo, Tresibia mankhwalawa amachepetsa zizindikiro zomwe zili pamwambazi poyerekeza ndi Lantus.
• Muyenera kuganiziranso za zovuta za mankhwala monga zotupa. Izi zimachitika kawirikawiri, koma zimatha kuchitika.
• Ngati mukufunikira kusintha kuchokera ku mankhwala a insulin ofanana ndi NPH, dziwani kuti mlingo wa mankhwalawa mukatha kudya ungafunikire kuchepetsedwa.

Kutenga nthawi yayitali insulin ya matenda a shuga a mtundu II

Chithandizo cha matenda a shuga a mtundu II nthawi zambiri chimayamba ndi kuyambitsa zakudya zoyenera komanso mankhwala amkamwa (Metformin, Siofor, Diabeteson, etc. ..). Komabe, pali zochitika zina pomwe madokotala amakakamizidwa kugwiritsa ntchito insulin.

Zofala kwambiri zalembedwa pansipa:

• Kusakwanira kwa mankhwala amkamwa, kulephera kukwaniritsa bwinobwino glycemia ndi glycated hemoglobin
• Contraindication pakamwa
• Kuzindikira matenda ashuga omwe ali ndi ziwonetsero zambiri za glycemic, kuchuluka kwa matenda
• Myocardial infarction, coronary angiography, sitiroko, matenda owopsa, opaleshoni
• Mimba

Mbiri yayitali ya insulin

Mlingo woyambirira nthawi zambiri amakhala mayunitsi 0,2 kg / thupi. Calculator iyi ndi yothandiza kwa anthu popanda kukana insulini, yokhala ndi chiwindi chokhazikika komanso impso. Mlingo wa insulin umayikidwa ndi dokotala wokha (!)

Kuphatikiza pa kutalika kwa nthawi yochitikira (yayitali kwambiri ndi degludec, yocheperako kwambiri ndi ma genetic engineer a insulin-isophan), mankhwalawa amasiyana maonekedwe. Pankhani ya insulin NPH, pachimake chiwonetserochi chimagawidwa nthawi yayitali ndipo chimachitika pakati pa maola 4 ndi 14 jakisoni. Analogue yogwira ntchito ya insulir yaigwira kwa nthawi yayitali imafika pachimake pakati pa maola 6 ndi 8 jekeseni, koma imakhala yochepa kwambiri komanso yochepa.

Insulin glargine chifukwa chake imatchedwa basal insulin. Kuphatikiza kwake m'magazi kumakhala kochepa kwambiri, kotero chiopsezo cha hypoglycemia ndichotsika kwambiri.

Mndandanda wazofananira

Mlendo wina adanenanso kuchuluka kwa anthu tsiku lililonse