Peringatan Keamanan

Patisiran produced no signs of embryo-fetal toxicity at dosages of up to 1.5 mg/kg in rats FDA Label. In rabbits given dosages of 0, 0.3, 1, and 2 mg/kg embryo-fetal and maternal toxicity were seen at mid and high dosages. No data exists in human subjects regarding risk during pregnancy.

Patisirant does not appear to be present in breast milk, however the lipid components of the liposomal dosage form are present FDA Label.

Patisirant is immunogenic with specific antibodies appearing in 3.6% of treated patients FDA Label. While there is no evidence of these antibodies reducing the efficacy of the drug, there is a risk of experiencing immunologic complications associated with the use of biologics.

Patisirant is known to reduce available vitamin A. Patients using the drug are at increased risk of vitamin A deficiency FDA Label.

Patisiran

DB14582

biotech approved investigational

Deskripsi

Patisiran is a first in class short interfering RNA for the treatment of patients with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis L4220. It is marketed as Onpattro which is formulated as patisiran within a liposome envelope for better delivery to the liver, where transthyretin is produced. The approval for Onpattro was granted to Alnylam Pharmaceuticals, Inc. in August of 2018. Onpattro has been granted Fast Track, Priority Review and Breakthrough Therapy, and Orphan Drug designations.

Struktur Molekul 2D

Struktur tidak tersedia

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Patisiran has a terminal elimination half-life of 3.2 ± 1.8 days [FDA Label].
Volume Distribusi The steady state volume of distribution of patisiran is 0.26 ± 0.20 L/kg observed with chronic dosing at 0.3 mg/kg every 3 weeks [FDA Label].
Klirens (Clearance) The total body clearance of patisiran is 3.0 ± 2.5 mL/h/kg [FDA Label].

Absorpsi

Patisiran follows a linear dose-proportional absorption curve FDA Label. Over 95% of administered drug remains with the liposomal complex which distributes primarily to the liver. With chronic dosing at 0.3 mg/kg every 3 weeks, steady state is reached by 24 weeks. The accumulation factor of the AUC is 3.2 with chronic dosing.

Metabolisme

Patisiran is metabolized to individual nucleotides and oligonucleotides of varying lengths by nucleases similarly to endogenous RNA FDA Label

Rute Eliminasi

Less than 1% is excreted through the urine. The bulk of the drug is broken down by nucleases FDA Label. No dosage adjustment is required in patients with mild hepatic impairment or mild to moderate renal impairment. No data exists for patients with severe to end-stage renal impairment or moderate to severe hepatic impairment.

Interaksi Obat

0 Data
Tidak ada data.

Target Protein

Transthyretin mRNA

Referensi & Sumber

Artikel (PubMed)
  • PMID: 27033334
    Butler JS, Chan A, Costelha S, Fishman S, Willoughby JL, Borland TD, Milstein S, Foster DJ, Goncalves P, Chen Q, Qin J, Bettencourt BR, Sah DW, Alvarez R, Rajeev KG, Manoharan M, Fitzgerald K, Meyers RE, Nochur SV, Saraiva MJ, Zimmermann TS: Preclinical evaluation of RNAi as a treatment for transthyretin-mediated amyloidosis. Amyloid. 2016 Jun;23(2):109-18. doi: 10.3109/13506129.2016.1160882. Epub 2016 Mar 31.
  • PMID: 29972753
    Adams D, Gonzalez-Duarte A, O'Riordan WD, Yang CC, Ueda M, Kristen AV, Tournev I, Schmidt HH, Coelho T, Berk JL, Lin KP, Vita G, Attarian S, Plante-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH 3rd, Kim BJ, Oh J, Parman Y, Sekijima Y, Hawkins PN, Solomon SD, Polydefkis M, Dyck PJ, Gandhi PJ, Goyal S, Chen J, Strahs AL, Nochur SV, Sweetser MT, Garg PP, Vaishnaw AK, Gollob JA, Suhr OB: Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018 Jul 5;379(1):11-21. doi: 10.1056/NEJMoa1716153.
  • PMID: 28824341
    Dana H, Chalbatani GM, Mahmoodzadeh H, Karimloo R, Rezaiean O, Moradzadeh A, Mehmandoost N, Moazzen F, Mazraeh A, Marmari V, Ebrahimi M, Rashno MM, Abadi SJ, Gharagouzlo E: Molecular Mechanisms and Biological Functions of siRNA. Int J Biomed Sci. 2017 Jun;13(2):48-57.

Contoh Produk & Brand

Produk: 3 • International brands: 0
Produk
  • Onpattro
    Injection, solution, concentrate • 2 mg/ml • Intravenous • EU • Approved
  • Onpattro
    Injection, lipid complex • 2 mg/1mL • Intravenous • US • Approved
  • Onpattro
    Solution • 2 mg / mL • Intravenous • Canada • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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