Peringatan Keamanan

There are no known cases of overdose with asparaginase Erwinia chrysanthemi.^L149 In clinical trials, the most common adverse effects were hypersensitivity reactions, pancreatic toxicity, blood clots, hemorrhage, and liver toxicity.^L34714 Pancreatitis occurs in 8-14% of pediatric patients, with adolescents at the highest risk for developing this adverse event. Pancreatitis typically occurs after the first few weeks of asparaginase administration, which suggests this complication occurs from an underlying predisposition rather than a cumulative drug effect.^A7464

Asparaginase Erwinia chrysanthemi

DB08886

biotech approved investigational

Deskripsi

Asparaginase Erwinia chrysanthemi is an asparaginase-specific enzyme derived from Erwinia chrysanthemi used as an anticancer agent. It works by depleting the stores of an important amino acid called asparagine, which is involved in DNA synthesis and cell survival of malignant cells, leading to cell death.^L1448 L-asparaginase was first identified in 1963,^A236344 and there are different formulations of L-asparaginase, including Asparaginase Escherichia coli and a pegylated form of this enzyme, Pegaspargase.^A7464 Asparaginase Erwinia chrysanthemi and Asparaginase Escherichia coli differ in their pharmacokinetic and immunogenic profiles;^L1452 thus, those who are allergic to Asparaginase Escherichia coli do not cross-react to Asparaginase Erwinia chrysanthemi.^A236344 Studies show that substitution of Erwinia asparaginase for E. coli-derived asparaginase following an allergic reaction has been safe and effective.^A236359

Asparaginase Erwinia chrysanthemi was first approved by the FDA in November 2011 to treat patients with acute lymphoblastic leukemia (ALL) who are allergic to E. coli-derived asparaginase: it has been used as part of multi-agent chemotherapy.^L149 In June 2021, the recombinant form of asparaginase Erwinia chrysanthemi was approved by the FDA as a component of a chemotherapy regimen to treat acute lymphoblastic leukemia and lymphoblastic lymphoma in adult and pediatric patients who are allergic to the E. coli-derived asparaginase.^L34714

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) The apparent half-life (%CV) of asparaginase _Erwinia chrysanthemi_ (recombinant)-rywn is 18.2 hours (16%).[L34719] Asparaginase _Erwinia chrysanthemi_ has a shorter half-life compared with the E. coli-derived preparations.[A7464]

Volume Distribusi The volume of distribution of asparaginase _Erwinia chrysanthemi_ can be up to 5 L/m2.[L1448] The geometric mean (%CV) apparent volume of distribution of asparaginase _Erwinia chrysanthemi_ (recombinant)-rywn was 1.48 L/m2 (49%).[L34719] While asparaginases are not detectable in cerebrospinal fluid, asparagine in cerebrospinal fluid is depleted with systemic administration of any formulation of asparaginases.[L1448]

Klirens (Clearance) The geometric mean (%CV) apparent clearance of asparaginase _Erwinia chrysanthemi_ (recombinant)-rywn is 0.31 L/hour/m2 (36%).[L34719]

Absorpsi

In patients two to 80 years of age, intramuscular administration of asparaginase Erwinia chrysanthemi 25,000 International Units (IU)/m² resulted in serum trough asparaginase concentrations ? 0.1 IU/mL at either 48-hour (n=35) or 72-hour (n=13) post third dose. 80% of patients evaluted at 48 hours and 38% of patients evaluated at 72 hours had serum asparaginase activity levels > 0.4 IU/mL.^L149 For asparaginase Erwinia chrysanthemi (recombinant)-rywn, the median t_max is 10 hours and the mean absolute bioavailability is 37% in healthy subjects.^L34719

Metabolisme

Metabolism of asparaginase Erwinia chrysanthemi has not been fully characterized; however, it is suspected to be metabolized into small peptides by catabolic pathways.^L34719

Rute Eliminasi

Trace amounts of asparaginases are found in urine.^L34719

Interaksi Obat

62 Data

Dexamethasone	The serum concentration of Dexamethasone can be increased when it is combined with Asparaginase Erwinia chrysanthemi.
Methotrexate	The therapeutic efficacy of Methotrexate can be decreased when used in combination with Asparaginase Erwinia chrysanthemi.
Imatinib	The risk or severity of liver damage can be increased when Asparaginase Erwinia chrysanthemi is combined with Imatinib.
Phenytoin	The therapeutic efficacy of Phenytoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Liothyronine	The therapeutic efficacy of Liothyronine can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Levothyroxine	The therapeutic efficacy of Levothyroxine can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Mephenytoin	The therapeutic efficacy of Mephenytoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Carbamazepine	The therapeutic efficacy of Carbamazepine can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Furosemide	The therapeutic efficacy of Furosemide can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Nitrofurantoin	The therapeutic efficacy of Nitrofurantoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Ethotoin	The therapeutic efficacy of Ethotoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Meclofenamic acid	The therapeutic efficacy of Meclofenamic acid can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Heparin	The therapeutic efficacy of Heparin can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Dantrolene	The therapeutic efficacy of Dantrolene can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Fosphenytoin	The therapeutic efficacy of Fosphenytoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Liotrix	The therapeutic efficacy of Liotrix can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Etofenamate	The therapeutic efficacy of Etofenamate can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Liothyronine I-131	The therapeutic efficacy of Liothyronine I-131 can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Neocitrullamon	The therapeutic efficacy of Neocitrullamon can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Allantoin	The therapeutic efficacy of Allantoin can be increased when used in combination with Asparaginase Erwinia chrysanthemi.
Pexidartinib	Asparaginase Erwinia chrysanthemi may increase the hepatotoxic activities of Pexidartinib.
Darbepoetin alfa	The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Asparaginase Erwinia chrysanthemi.
Erythropoietin	The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Asparaginase Erwinia chrysanthemi.
Peginesatide	The risk or severity of Thrombosis can be increased when Peginesatide is combined with Asparaginase Erwinia chrysanthemi.
Methoxy polyethylene glycol-epoetin beta	The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Asparaginase Erwinia chrysanthemi.
Valoctocogene roxaparvovec	The therapeutic efficacy of Valoctocogene roxaparvovec can be decreased when used in combination with Asparaginase Erwinia chrysanthemi.
Lidocaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Lidocaine.
Ropivacaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Ropivacaine.
Bupivacaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Bupivacaine.
Cinchocaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Cinchocaine.
Dyclonine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Dyclonine.
Procaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Procaine.
Prilocaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Prilocaine.
Proparacaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Proparacaine.
Meloxicam	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Meloxicam.
Oxybuprocaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Oxybuprocaine.
Cocaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Cocaine.
Mepivacaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Mepivacaine.
Levobupivacaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Levobupivacaine.
Diphenhydramine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Diphenhydramine.
Benzocaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Benzocaine.
Chloroprocaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Chloroprocaine.
Phenol	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Phenol.
Tetrodotoxin	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Tetrodotoxin.
Benzyl alcohol	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Benzyl alcohol.
Capsaicin	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Capsaicin.
Etidocaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Etidocaine.
Articaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Articaine.
Tetracaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Tetracaine.
Propoxycaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Propoxycaine.
Pramocaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Pramocaine.
Butamben	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Butamben.
Butacaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Butacaine.
Oxetacaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Oxetacaine.
Ethyl chloride	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Ethyl chloride.
Butanilicaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Butanilicaine.
Metabutethamine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Metabutethamine.
Quinisocaine	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Quinisocaine.
Ambroxol	The risk or severity of methemoglobinemia can be increased when Asparaginase Erwinia chrysanthemi is combined with Ambroxol.
Etrasimod	The risk or severity of immunosuppression can be increased when Asparaginase Erwinia chrysanthemi is combined with Etrasimod.
Leflunomide	The risk or severity of liver damage can be increased when Asparaginase Erwinia chrysanthemi is combined with Leflunomide.
Teriflunomide	The risk or severity of liver damage can be increased when Asparaginase Erwinia chrysanthemi is combined with Teriflunomide.

Referensi & Sumber

Artikel (PubMed)

PMID: 20824725
Pieters R, Hunger SP, Boos J, Rizzari C, Silverman L, Baruchel A, Goekbuget N, Schrappe M, Pui CH: L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer. 2011 Jan 15;117(2):238-49. doi: 10.1002/cncr.25489. Epub 2010 Sep 7.
PMID: 25098829
Salzer WL, Asselin BL, Plourde PV, Corn T, Hunger SP: Development of asparaginase Erwinia chrysanthemi for the treatment of acute lymphoblastic leukemia. Ann N Y Acad Sci. 2014 Nov;1329:81-92. doi: 10.1111/nyas.12496. Epub 2014 Aug 5.
PMID: 27440950
Egler RA, Ahuja SP, Matloub Y: L-asparaginase in the treatment of patients with acute lymphoblastic leukemia. J Pharmacol Pharmacother. 2016 Apr-Jun;7(2):62-71. doi: 10.4103/0976-500X.184769.

Link

Contoh Produk & Brand

Produk: 5 • International brands: 1

Produk

Enrylaze

Injection, solution • 10 mg/0.5ml • - • EU • Approved
Erwinase

Injection, powder, lyophilized, for solution • 10000 [iU]/1mL • Intramuscular; Intravenous • US
Erwinase

Powder, for solution • 10000 unit • Intramuscular; Intravenous; Subcutaneous • Canada • Approved
Erwinaze

Injection, powder, lyophilized, for solution • 10000 [iU]/1mL • Intramuscular; Intravenous • US • Approved
Rylaze

Solution • 10 mg / 0.5 mL • Intramuscular • Canada • Approved

International Brands

Rylaze — Jazz Pharmaceuticals plc

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.