Peringatan Keamanan

There is limited information regarding the overdosage and acute toxicity (LD50) of elafibranor.

Elafibranor

DB05187

small molecule approved investigational

Deskripsi

Elafibranor is a dual peroxisome proliferator-activated receptor (PPAR) ? and ?/? agonist A263833 that works to inhibit bile acid synthesis.L50768 On June 10, 2024, elafibranor was granted accelerated approval by the FDA for the treatment of primary biliary cholangitis (PBC).L50773 The drug was also approved by the EMA on September 23, 2024.L51878

Struktur Molekul 2D

Berat 384.49
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Following a single 80 mg dose under fasted conditions, median elimination half-life was 70.2 hours (range 37.1 to 92.2 hours) for elafibranor, and 15.4 hours (range 9.39 to 21.7 hours) for major active metabolite GFT1007.[L50768]
Volume Distribusi The mean apparent volume of distribution (Vd/F) of elafibranor in healthy subjects was 4731 L, following a single dose of 80 mg under fasted conditions.[L50768]
Klirens (Clearance) The mean apparent total clearance (CL/F) of elafibranor was 50.0 L/h after a single 80 mg dose under fasted conditions.[L50768]

Absorpsi

Following once-daily dosing, the steady state of elafibranor and its major active metabolite, GFT1007, was achieved within seven and fourteen days, respectively.L50768 The mean (SD) Cmax at steady state was 802 (443) ng/mL for elafibranor and 2058 (459) ng/mL for GFT1007.L50768 The mean (SD) AUC was 3758 (1749) ng x h/mL for elafibranor and 11985 (7149) ng x h/mL for GFT1007.L50768 Following once-daily dosing of 80 mg in patients with PBC, the median time to peak plasma concentrations (Tmax) of elafibranor and GFT1007 was 1.25 hours (range: 0.5-2 hours).L50768 When administered with a high-fat and high-calorie meal, Tmax was delayed by 30 minutes for elafibranor and by 1-hour for GFT1007 compared to in fasted conditions. Under fed condition, mean Cmax and AUC of elafibranor decreased by 50% and 15% respectively and mean Cmax of GFT1007 decreased by 30%, but the AUC was not affected compared to fasted conditions. The difference was not clinically meaningful.L50768

Metabolisme

Elafibranor is extensively metabolized to form a major active metabolite, GFT1007, the chemical structure of which has not yet been characterized. The mean systemic exposure (AUC) to GFT1007 was 3.2-fold higher than that of elafibranor at steady state. GFT3351, an acyl glucuronide conjugate, is a major inactive metabolite that consists of four stereoisomers. In vitro studies showed that elafibranor was metabolized by 15-ketoprostaglandin 13-? reductase (PTGR1), a cytosolic enzyme, to form GFT1007. Elafibranor was also metabolized by CYP2J2, UGT1A3, UGT1A4, and UGT2B7. GFT1007 was further metabolized by CYP2C8, UGT1A3, and UGT2B7.L50768

Rute Eliminasi

Following a single 120 mg oral dose (1.5 times the recommended dose) of 14C-radiolabelled elafibranor in healthy subjects, approximately 77.1% of the dose was recovered in feces, primarily as elafibranor (56.7% of the administered dose) and its major metabolite GFT1007 (6.08% of the administered dose). Approximately 19.3% was recovered in urine, primarily as glucuronide conjugate GFT3351 (11.8% of the administered dose). A negligible amount of unchanged elafibranor or GFT1007 was detectable in the urine. Biliary excretion of elafibranor in humans was suggested by the excretion of 60% of orally administered elafibranor in the bile of rats.L50768

Interaksi Makanan

1 Data
  • 1. Take with or without food. A high-fat and high-calorie meal delays Tmax and decreases Cmax and AUC, but not to a clinically significant extent.

Interaksi Obat

228 Data
Diethylstilbestrol The metabolism of Diethylstilbestrol can be decreased when combined with Elafibranor.
Etonogestrel The metabolism of Etonogestrel can be decreased when combined with Elafibranor.
Desogestrel The metabolism of Desogestrel can be decreased when combined with Elafibranor.
Megestrol acetate The metabolism of Megestrol acetate can be decreased when combined with Elafibranor.
Levonorgestrel The metabolism of Levonorgestrel can be decreased when combined with Elafibranor.
Progesterone The metabolism of Progesterone can be decreased when combined with Elafibranor.
Medroxyprogesterone acetate The metabolism of Medroxyprogesterone acetate can be decreased when combined with Elafibranor.
Norethisterone The metabolism of Norethisterone can be decreased when combined with Elafibranor.
Estradiol The metabolism of Estradiol can be decreased when combined with Elafibranor.
Ethynodiol diacetate The metabolism of Ethynodiol diacetate can be decreased when combined with Elafibranor.
Mifepristone The metabolism of Mifepristone can be decreased when combined with Elafibranor.
Norgestimate The metabolism of Norgestimate can be decreased when combined with Elafibranor.
Ethinylestradiol The metabolism of Ethinylestradiol can be decreased when combined with Elafibranor.
Mestranol The metabolism of Mestranol can be decreased when combined with Elafibranor.
Drospirenone The metabolism of Drospirenone can be decreased when combined with Elafibranor.
Estrone sulfate The metabolism of Estrone sulfate can be decreased when combined with Elafibranor.
Octylphenoxy polyethoxyethanol The metabolism of Octylphenoxy polyethoxyethanol can be decreased when combined with Elafibranor.
Cyproterone acetate The metabolism of Cyproterone acetate can be decreased when combined with Elafibranor.
Trestolone The metabolism of Trestolone can be decreased when combined with Elafibranor.
Norelgestromin The metabolism of Norelgestromin can be decreased when combined with Elafibranor.
Gestodene The metabolism of Gestodene can be decreased when combined with Elafibranor.
Hydroxyprogesterone caproate The metabolism of Hydroxyprogesterone caproate can be decreased when combined with Elafibranor.
Nonoxynol-9 The metabolism of Nonoxynol-9 can be decreased when combined with Elafibranor.
Ulipristal The metabolism of Ulipristal can be decreased when combined with Elafibranor.
Dienogest The metabolism of Dienogest can be decreased when combined with Elafibranor.
Norethynodrel The metabolism of Norethynodrel can be decreased when combined with Elafibranor.
Norgestrel The metabolism of Norgestrel can be decreased when combined with Elafibranor.
Cloprostenol The metabolism of Cloprostenol can be decreased when combined with Elafibranor.
Gestrinone The metabolism of Gestrinone can be decreased when combined with Elafibranor.
Nomegestrol The metabolism of Nomegestrol can be decreased when combined with Elafibranor.
Lynestrenol The metabolism of Lynestrenol can be decreased when combined with Elafibranor.
Gossypol The metabolism of Gossypol can be decreased when combined with Elafibranor.
Ormeloxifene The metabolism of Ormeloxifene can be decreased when combined with Elafibranor.
Chlormadinone The metabolism of Chlormadinone can be decreased when combined with Elafibranor.
Norgestrienone The metabolism of Norgestrienone can be decreased when combined with Elafibranor.
Quingestanol The metabolism of Quingestanol can be decreased when combined with Elafibranor.
Demegestone The metabolism of Demegestone can be decreased when combined with Elafibranor.
Etynodiol The metabolism of Etynodiol can be decreased when combined with Elafibranor.
Testosterone enanthate The metabolism of Testosterone enanthate can be decreased when combined with Elafibranor.
Estradiol benzoate The metabolism of Estradiol benzoate can be decreased when combined with Elafibranor.
Estradiol cypionate The metabolism of Estradiol cypionate can be decreased when combined with Elafibranor.
Estradiol valerate The metabolism of Estradiol valerate can be decreased when combined with Elafibranor.
Nomegestrol acetate The metabolism of Nomegestrol acetate can be decreased when combined with Elafibranor.
Segesterone acetate The metabolism of Segesterone acetate can be increased when combined with Elafibranor.
Norethindrone enanthate The metabolism of Norethindrone enanthate can be decreased when combined with Elafibranor.
Pravastatin The risk or severity of myopathy can be increased when Elafibranor is combined with Pravastatin.
Lovastatin The risk or severity of myopathy can be increased when Elafibranor is combined with Lovastatin.
Cerivastatin The risk or severity of myopathy can be increased when Elafibranor is combined with Cerivastatin.
Simvastatin The risk or severity of myopathy can be increased when Elafibranor is combined with Simvastatin.
Atorvastatin The risk or severity of myopathy can be increased when Elafibranor is combined with Atorvastatin.
Fluvastatin The risk or severity of myopathy can be increased when Elafibranor is combined with Fluvastatin.
Rosuvastatin The risk or severity of myopathy can be increased when Elafibranor is combined with Rosuvastatin.
Mevastatin The risk or severity of myopathy can be increased when Elafibranor is combined with Mevastatin.
Pitavastatin The risk or severity of myopathy can be increased when Elafibranor is combined with Pitavastatin.
Rifampin The metabolism of Elafibranor can be increased when combined with Rifampin.
Colestipol Colestipol can cause a decrease in the absorption of Elafibranor resulting in a reduced serum concentration and potentially a decrease in efficacy.
Sevelamer Sevelamer can cause a decrease in the absorption of Elafibranor resulting in a reduced serum concentration and potentially a decrease in efficacy.
Colesevelam Colesevelam can cause a decrease in the absorption of Elafibranor resulting in a reduced serum concentration and potentially a decrease in efficacy.
Cholestyramine Cholestyramine can cause a decrease in the absorption of Elafibranor resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aripiprazole The metabolism of Aripiprazole can be increased when combined with Elafibranor.
Aripiprazole lauroxil The metabolism of Aripiprazole lauroxil can be increased when combined with Elafibranor.
Ifosfamide The metabolism of Ifosfamide can be increased when combined with Elafibranor.
Perampanel The metabolism of Perampanel can be increased when combined with Elafibranor.
Warfarin The metabolism of Warfarin can be increased when combined with Elafibranor.
Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Elafibranor.
(R)-warfarin The metabolism of (R)-warfarin can be increased when combined with Elafibranor.
R,S-Warfarin alcohol The metabolism of R,S-Warfarin alcohol can be increased when combined with Elafibranor.
S,R-Warfarin alcohol The metabolism of S,R-Warfarin alcohol can be increased when combined with Elafibranor.
(S)-Warfarin The metabolism of (S)-Warfarin can be increased when combined with Elafibranor.
Erlotinib The serum concentration of Erlotinib can be decreased when it is combined with Elafibranor.
Azithromycin The metabolism of Azithromycin can be increased when combined with Elafibranor.
Ziprasidone The metabolism of Ziprasidone can be increased when combined with Elafibranor.
Methysergide The metabolism of Methysergide can be increased when combined with Elafibranor.
Terfenadine The metabolism of Terfenadine can be increased when combined with Elafibranor.
Meperidine The metabolism of Meperidine can be increased when combined with Elafibranor.
Chlorpromazine The metabolism of Chlorpromazine can be increased when combined with Elafibranor.
Albendazole The metabolism of Albendazole can be increased when combined with Elafibranor.
Cephalexin The metabolism of Cephalexin can be increased when combined with Elafibranor.
Doxazosin The metabolism of Doxazosin can be increased when combined with Elafibranor.
Cisapride The metabolism of Cisapride can be increased when combined with Elafibranor.
Astemizole The metabolism of Astemizole can be increased when combined with Elafibranor.
Fenofibrate The metabolism of Fenofibrate can be increased when combined with Elafibranor.
Atazanavir The metabolism of Atazanavir can be increased when combined with Elafibranor.
Pimozide The metabolism of Pimozide can be increased when combined with Elafibranor.
Amiodarone The metabolism of Amiodarone can be increased when combined with Elafibranor.
Fosphenytoin The metabolism of Fosphenytoin can be increased when combined with Elafibranor.
Allylestrenol The metabolism of Allylestrenol can be increased when combined with Elafibranor.
Zuclopenthixol The metabolism of Zuclopenthixol can be increased when combined with Elafibranor.
Roflumilast The metabolism of Roflumilast can be increased when combined with Elafibranor.
Pretomanid The metabolism of Pretomanid can be increased when combined with Elafibranor.
Cobimetinib The metabolism of Cobimetinib can be increased when combined with Elafibranor.
Pimavanserin The metabolism of Pimavanserin can be increased when combined with Elafibranor.
Lacosamide The metabolism of Lacosamide can be increased when combined with Elafibranor.
Fosaprepitant The metabolism of Fosaprepitant can be increased when combined with Elafibranor.
Lomitapide The metabolism of Lomitapide can be increased when combined with Elafibranor.
Linagliptin The metabolism of Linagliptin can be increased when combined with Elafibranor.
Vorapaxar The metabolism of Vorapaxar can be increased when combined with Elafibranor.
Suvorexant The metabolism of Suvorexant can be increased when combined with Elafibranor.
Netupitant The metabolism of Netupitant can be increased when combined with Elafibranor.
Idelalisib The metabolism of Idelalisib can be increased when combined with Elafibranor.

Target Protein

Peroxisome proliferator-activated receptor alpha PPARA
Peroxisome proliferator-activated receptor delta PPARD
Peroxisome proliferator-activated receptor gamma PPARG

Referensi & Sumber

Artikel (PubMed)
  • PMID: 26874076
    Ratziu V, Harrison SA, Francque S, Bedossa P, Lehert P, Serfaty L, Romero-Gomez M, Boursier J, Abdelmalek M, Caldwell S, Drenth J, Anstee QM, Hum D, Hanf R, Roudot A, Megnien S, Staels B, Sanyal A: Elafibranor, an Agonist of the Peroxisome Proliferator-Activated Receptor-alpha and -delta, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. Gastroenterology. 2016 May;150(5):1147-1159.e5. doi: 10.1053/j.gastro.2016.01.038. Epub 2016 Feb 11.
  • PMID: 37783154
    Zhang M, Barroso E, Ruart M, Pena L, Peyman M, Aguilar-Recarte D, Montori-Grau M, Rada P, Cugat C, Montironi C, Zarei M, Jurado-Aguilar J, Camins A, Balsinde J, Valverde AM, Wahli W, Palomer X, Vazquez-Carrera M: Elafibranor upregulates the EMT-inducer S100A4 via PPARbeta/delta. Biomed Pharmacother. 2023 Nov;167:115623. doi: 10.1016/j.biopha.2023.115623. Epub 2023 Sep 30.
  • PMID: 21816979
    Cariou B, Zair Y, Staels B, Bruckert E: Effects of the new dual PPAR alpha/delta agonist GFT505 on lipid and glucose homeostasis in abdominally obese patients with combined dyslipidemia or impaired glucose metabolism. Diabetes Care. 2011 Sep;34(9):2008-14. doi: 10.2337/dc11-0093. Epub 2011 Aug 4.

Contoh Produk & Brand

Produk: 1 • International brands: 0
Produk
  • Iqirvo
    Tablet, film coated • 80 mg/1 • Oral • US • Approved

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