Peringatan Keamanan

There is no information on the LD50 value of inclisiran. There were no clinically relevant adverse reactions in healthy volunteers who received inclisiran at doses up to three times the therapeutic dose. If an overdose is suspected, symptomatic and supportive treatments should be initiated.L30468

Inclisiran

DB14901

biotech approved investigational

Deskripsi

Inclisiran is a long-acting, synthetic small interfering RNA (siRNA) directed against proprotein convertase subtilisin-kexin type 9 (PCSK9), which is a serine protease that regulates plasma low-density lipoprotein cholesterol (LDL-C) levels. By binding to PCSK9 messenger RNA, inclisiran prevents protein translation of PCSK9, leading to decreased concentrations of PCSK9 and plasma concentrations of LDL cholesterol.A225953,A225958 Lowering circulating plasma LDL-C levels offers an additional benefit of reducing the risk of cardiovascular disease (CVD) and improving cardiovascular outcomes, as hypercholesterolemia is a major known risk factor for CVD.A225953,A225958

On December 11, 2020, the European Commission (EC) granted authorization for marketing inclisiran as the first and only approved siRNA for the treatment of adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia, alone or in combination with other lipid-lowering therapies.L28178 Inclisiran was later approved by the FDA on December 22, 2021, for the treatment of heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease in adults.L39593 It is marketed under the trade name Leqvio.

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The terminal elimination half-life of inclisiran is approximately 9 hours.[L30468]
Volume Distribusi The apparent volume of distribution was approximately 500 L following subcutaneous administration of a single 284 mg dose of inclisiran in healthy adults. According to non-clinical studies, inclisiran is highly taken up by the liver.[L30468]
Klirens (Clearance) There is limited information on the clearance rate of inclisiran.

Absorpsi

After uptake into the liver, inclisiran has a long duration of action. Following subcutaneous administration of a single dose ranging from 24 mg to 756 mg, systemic exposure to inclisiran increased in a dose-proportional manner. The mean Cmax was 509 ng/mL and the Tmax was approximately 4 hours after the administration of 284 mg inclisiran. The mean AUC0-inf was 7980 ng x h/mL. After 48 hours of dosing, drug plasma concentrations were undetectable. Pharmacokinetic findings following a single-dose administration of inclisiran were comparable to inclisiran administered in multiple doses.L30468

Metabolisme

Inclisiran is metabolized by nucleases to form smaller nucleotides of varying lengths. It is not anticipated to be a substrate for cytochrome P450 enzymes.L30468

Rute Eliminasi

About 16% of the total dose of inclisiran is cleared through the kidney.L30468

Interaksi Obat

0 Data
Tidak ada data.

Target Protein

Proprotein convertase subtilisin/kexin type 9 PCSK9

Referensi & Sumber

Artikel (PubMed)
  • PMID: 30011788
    Kosmas CE, Munoz Estrella A, Sourlas A, Silverio D, Hilario E, Montan PD, Guzman E: Inclisiran: A New Promising Agent in the Management of Hypercholesterolemia. Diseases. 2018 Jul 13;6(3). pii: diseases6030063. doi: 10.3390/diseases6030063.
  • PMID: 31782112
    German CA, Shapiro MD: Small Interfering RNA Therapeutic Inclisiran: A New Approach to Targeting PCSK9. BioDrugs. 2020 Feb;34(1):1-9. doi: 10.1007/s40259-019-00399-6.
  • PMID: 32749892
    Doggrell SA: Inclisiran, the billion-dollar drug, to lower LDL cholesterol - is it worth it? Expert Opin Pharmacother. 2020 Nov;21(16):1971-1974. doi: 10.1080/14656566.2020.1799978. Epub 2020 Aug 4.
  • PMID: 3621516
    Goldstein JL, Brown MS: Regulation of low-density lipoprotein receptors: implications for pathogenesis and therapy of hypercholesterolemia and atherosclerosis. Circulation. 1987 Sep;76(3):504-7. doi: 10.1161/01.cir.76.3.504.
  • PMID: 19342379
    Pratt AJ, MacRae IJ: The RNA-induced silencing complex: a versatile gene-silencing machine. J Biol Chem. 2009 Jul 3;284(27):17897-901. doi: 10.1074/jbc.R900012200. Epub 2009 Apr 1.
  • PMID: 30487231
    Leiter LA, Teoh H, Kallend D, Wright RS, Landmesser U, Wijngaard PLJ, Kastelein JJP, Ray KK: Inclisiran Lowers LDL-C and PCSK9 Irrespective of Diabetes Status: The ORION-1 Randomized Clinical Trial. Diabetes Care. 2019 Jan;42(1):173-176. doi: 10.2337/dc18-1491. Epub 2018 Nov 28.
  • PMID: 32766688
    Cupido AJ, Kastelein JJP: Inclisiran for the treatment of hypercholesterolaemia: implications and unanswered questions from the ORION trials. Cardiovasc Res. 2020 Sep 1;116(11):e136-e139. doi: 10.1093/cvr/cvaa212.

Contoh Produk & Brand

Produk: 4 • International brands: 1
Produk
  • Leqvio
    Injection, solution • 284 mg/1.5ml • Subcutaneous • EU • Approved
  • Leqvio
    Injection, solution • 284 mg/1.5mL • Subcutaneous • US • Approved
  • Leqvio
    Injection, solution • 284 mg/1.5ml • Subcutaneous • EU • Approved
  • Leqvio
    Solution • 284 mg / 1.5 mL • Subcutaneous • Canada • Approved
International Brands
  • Leqvio — Novartis

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