Peringatan Keamanan

In preclinical safety studies, there was a change in reported systolic pressure after 2-weeks of multiple dosing.^L1107 Thrombus formation, cardiovascular, neurological or respiratory effects are not expected to be a safety concern.^L1108

Turoctocog alfa

DB09109

biotech approved investigational

Deskripsi

Turoctocog alfa is a recombinant factor VIII (rFVIII) with a truncated B-domain made from the sequence coding for 10 amino acids from the N-terminus and 11 amino acids from the C-terminus of the naturally occurring B-domain. Turoctocog alfa is produced in Chinese hamster ovary (CHO) cells without addition of any human- or animal-derived materials. During secretion, some rFVIII molecules are cleaved at the C-terminal of the heavy chain (HC) at amino acid 720, and a monoclonal antibody binding C-terminal to this position is used in the purification process allowing isolation of the intact rFVIII.^A31504 It was developped by Novo Nordisk and FDA approved in October 16, 2013.^L1104

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) In pre-clinical studies, turoctocog half-life was reported to be 16 hours.[A31506] In knockout mice there are reports of half-life of 7-8 hours.[L1108]

Volume Distribusi In pre-clinical studies, turoctocog distribution was studied based on a two model compartment and it resulted in 59 ml/kg in the central compartment and 13 ml/kg in the peripheral compartment. It also presented an inter-compartmental flow of 0.66 ml/hour kg.[A31506]

Klirens (Clearance) In pre-clinical studies, turoctocog clearance was reported to be 6.5 ml/hour kg.[A31506]

Absorpsi

In pre-clinical studies, the absorption half-life was reported wot be 5.4 hours.^A31506 The absorption profile varies depending on the age of the patient where the AUC is 9.92, 11.09 and 15.26 IU hour/ml for the age range of 0-6 years, 6-12 years and over 12 years old respectively. The Cmax according to the different age groups is 1, 1.07 and 1.226 IU/ml for the age range of 0-6 years, 6-12 years and over 12 years old respectively.^L1107

Metabolisme

Turoctocog alfa is expected to be cleaved by proteolysis into small individual aminoacids that constitute them after receptor mediated cell endocytosis.^L1108

Rute Eliminasi

After intravenous administration of turoctocog alfa, the time for complete elimination of the blood plasma is of 50-55 hours. Due to the fact that this drug is a 166 kDa, it is thought that it will be eliminated by tissue mechanisms such as receptor mediated endocytosis followed by catabolism rather than hepatic metabolism and renal excretion.^L1108

Interaksi Obat

92 Data

Aminocaproic acid	The risk or severity of adverse effects can be increased when Aminocaproic acid is combined with Turoctocog alfa.
Alpha-1-proteinase inhibitor	Alpha-1-proteinase inhibitor may increase the thrombogenic activities of Turoctocog alfa.
Menadione	Menadione may increase the thrombogenic activities of Turoctocog alfa.
Tranexamic acid	Tranexamic acid may increase the thrombogenic activities of Turoctocog alfa.
Aprotinin	Aprotinin may increase the thrombogenic activities of Turoctocog alfa.
Hydrogen peroxide	Hydrogen peroxide may increase the thrombogenic activities of Turoctocog alfa.
Aminomethylbenzoic acid	Aminomethylbenzoic acid may increase the thrombogenic activities of Turoctocog alfa.
Camostat	Camostat may increase the thrombogenic activities of Turoctocog alfa.
Menadione bisulfite	Menadione bisulfite may increase the thrombogenic activities of Turoctocog alfa.
Monteplase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Monteplase.
Lepirudin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Lepirudin.
Bivalirudin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Bivalirudin.
Alteplase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Alteplase.
Urokinase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Urokinase.
Reteplase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Reteplase.
Anistreplase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Anistreplase.
Tenecteplase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Tenecteplase.
Abciximab	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Abciximab.
Drotrecogin alfa	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Drotrecogin alfa.
Streptokinase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Streptokinase.
Dicoumarol	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Dicoumarol.
Argatroban	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Argatroban.
Ardeparin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Ardeparin.
Phenindione	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Phenindione.
Fondaparinux	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Fondaparinux.
Warfarin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Warfarin.
Pentosan polysulfate	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Pentosan polysulfate.
Phenprocoumon	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Phenprocoumon.
Dipyridamole	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Dipyridamole.
Heparin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Heparin.
Enoxaparin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Enoxaparin.
Epoprostenol	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Epoprostenol.
Acenocoumarol	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Acenocoumarol.
4-hydroxycoumarin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with 4-hydroxycoumarin.
Coumarin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Coumarin.
Ximelagatran	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Ximelagatran.
Desmoteplase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Desmoteplase.
Defibrotide	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Defibrotide.
Ancrod	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Ancrod.
Beraprost	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Beraprost.
Prasugrel	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Prasugrel.
Rivaroxaban	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Rivaroxaban.
Sulodexide	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Sulodexide.
Idraparinux	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Idraparinux.
Cangrelor	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Cangrelor.
Astaxanthin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Astaxanthin.
Apixaban	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Apixaban.
Otamixaban	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Otamixaban.
Amediplase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Amediplase.
Dabigatran etexilate	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Dabigatran etexilate.
Danaparoid	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Danaparoid.
Dalteparin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Dalteparin.
Tinzaparin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Tinzaparin.
(R)-warfarin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with (R)-warfarin.
Ethyl biscoumacetate	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Ethyl biscoumacetate.
Nadroparin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Nadroparin.
Triflusal	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Triflusal.
Ticagrelor	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Ticagrelor.
Ditazole	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Ditazole.
Vorapaxar	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Vorapaxar.
Edoxaban	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Edoxaban.
Sodium citrate	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Sodium citrate.
Dextran	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Dextran.
Bemiparin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Bemiparin.
Parnaparin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Parnaparin.
Desirudin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Desirudin.
Antithrombin Alfa	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Antithrombin Alfa.
Protein C	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Protein C.
Antithrombin III human	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Antithrombin III human.
Letaxaban	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Letaxaban.
Darexaban	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Darexaban.
Betrixaban	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Betrixaban.
Nafamostat	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Nafamostat.
Gabexate	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Gabexate.
Fluindione	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Fluindione.
Protein S human	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Protein S human.
Brinase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Brinase.
Clorindione	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Clorindione.
Diphenadione	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Diphenadione.
Tioclomarol	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Tioclomarol.
Melagatran	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Melagatran.
Saruplase	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Saruplase.
(S)-Warfarin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with (S)-Warfarin.
Tocopherylquinone	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Tocopherylquinone.
Dabigatran	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Dabigatran.
Semuloparin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Semuloparin.
Troxerutin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Troxerutin.
Edetic acid	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Edetic acid.
Reviparin	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Reviparin.
Dermatan sulfate	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Dermatan sulfate.
SR-123781A	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with SR-123781A.
Limaprost	The therapeutic efficacy of Turoctocog alfa can be decreased when used in combination with Limaprost.

Target Protein

Coagulation factor IX F9

Coagulation factor X F10

Prothrombin F2

Referensi & Sumber

Artikel (PubMed)

PMID: 24797664
Ezban M, Vad K, Kjalke M: Turoctocog alfa (NovoEight(R))--from design to clinical proof of concept. Eur J Haematol. 2014 Nov;93(5):369-76. doi: 10.1111/ejh.12366. Epub 2014 May 28.
PMID: 29261993
Salen P, Babiker HM: Hemophilia A .
PMID: 22812621
Agerso H, Stennicke HR, Pelzer H, Olsen EN, Merricks EP, Defriess NA, Nichols TC, Ezban M: Pharmacokinetics and pharmacodynamics of turoctocog alfa and N8-GP in haemophilia A dogs. Haemophilia. 2012 Nov;18(6):941-7. doi: 10.1111/j.1365-2516.2012.02896.x. Epub 2012 Jul 20.
PMID: 26761578
Ahmadian H, Hansen EB, Faber JH, Sejergaard L, Karlsson J, Bolt G, Hansen JJ, Thim L: Molecular design and downstream processing of turoctocog alfa (NovoEight), a B-domain truncated factor VIII molecule. Blood Coagul Fibrinolysis. 2016 Jul;27(5):568-75. doi: 10.1097/MBC.0000000000000477.
PMID: 25848213
Takedani H, Hirose J: Turoctocog alfa: an evidence-based review of its potential in the treatment of hemophilia A. Drug Des Devel Ther. 2015 Mar 24;9:1767-72. doi: 10.2147/DDDT.S57967. eCollection 2015.

Link

Contoh Produk & Brand

Produk: 12 • International brands: 0

Produk

Novoeight

Injection, powder, for solution • 250 IU • Intravenous • EU • Approved
Novoeight

Injection, powder, for solution • 500 IU • Intravenous • EU • Approved
Novoeight

Injection, powder, for solution • 1000 IU • Intravenous • EU • Approved
Novoeight

Injection, powder, for solution • 1500 IU • Intravenous • EU • Approved
Novoeight

Injection, powder, for solution • 2000 IU • Intravenous • EU • Approved
Novoeight

Injection, powder, for solution • 3000 IU • Intravenous • EU • Approved
Zonovate

Kit; Powder, for solution • 250 unit / vial • Intravenous • Canada • Approved
Zonovate

Kit; Powder, for solution • 500 unit / vial • Intravenous • Canada • Approved

Menampilkan 8 dari 12 produk.

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.