Peringatan Keamanan

PBC patients who received five-times the recommended dosage or 20-times the recommended dosage of seladelpar experienced an increase in liver transaminases, muscle pain, and/or elevations in creatine phosphokinase, which resolved upon seladelpar discontinuation. There is no specific treatment for overdose with seladelpar. General supportive care of the patient is indicated, as appropriate. If indicated, elimination of unabsorbed drug should be achieved by emesis or gastric lavage; usual precautions should be observed to maintain the airway. Because seladelpar is highly bound to plasma proteins, hemodialysis should not be considered.L51149

Seladelpar

DB12390

small molecule approved investigational

Deskripsi

Seladelpar is a peroxisome proliferator-activated receptor (PPAR)-delta (?) agonist. Seladelpar is a single enantiomer of the R-configuration.L51149 On August 14, 2024, seladelpar was granted accelerated approval by the FDA for the treatment of primary biliary cholangitis,L51154 which is a condition associated with aberrant bile acid metabolism. Seladelpar works to block bile acid synthesis.A264234

Struktur Molekul 2D

Berat 444.47
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) Following administration of a single dose of 10 mg seladelpar in healthy subjects, mean elimination half-life was six hours for seladelpar. In PBC patients, the half-life range was 3.8 to 6.7 hours for seladelpar.[L51149]
Volume Distribusi Seladelpar steady state apparent volume of distribution was approximately 133.2 L.[L51149]
Klirens (Clearance) The apparent oral clearance of seladelpar is 12 L/h.[L51149]

Absorpsi

Following a single dose administration, seladelpar systemic exposure increased dose-proportionally from 2 mg (0.2 times the recommended dosage) to 15 mg (1.5 times the recommended dosage) and greater than dose proportionally at higher doses. For a dose increase from 10 mg to 200 mg (20 times the recommended dosage), mean Cmax and mean AUC for seladelpar increased 70-fold and 27-fold, respectively.L51149 Following once daily dosing, seladelpar steady-state was achieved by day 4 and AUC increase was less than 30%. In PBC patients, mean (SD) Cmax and AUC for seladelpar was 103 (29.3) ng/mL and 902 (238) ng x h/mL, respectively at steady-state following once daily dosing of 10 mg. The median time to peak concentration (Tmax) was 1.5 hours for seladelpar. No clinically significant differences in seladelpar pharmacokinetics were observed following administration of a high-fat meal in healthy subjects.L51149

Metabolisme

Seladelpar is primarily metabolized in vitro by CYP2C9 and to a lesser extent by CYP2C8 and CYP3A4, resulting in the three major metabolites: seladelpar sulfoxide (M1), desethyl-seladelpar (M2), and desethyl-seladelpar sulfoxide (M3). The metabolite-to-parent AUC ratios were 0.36, 2.32 and 0.63 for M1, M2 and M3, respectively. Median Tmax for metabolites were 10 hours for M1 and 4 hours for M2 and M3. None of the major metabolites have pharmacological activity.L51149

Rute Eliminasi

Seladelpar is primarily eliminated in urine as metabolites. Following a single oral dose of 10 mg radiolabeled seladelpar in humans, approximately 73.4% of the dose was recovered in urine (less than 0.01% unchanged) and 19.5% in feces (2.02% unchanged) within 216 hours. Biliary excretion of seladelpar was suggested by an animal study.L51149

Interaksi Makanan

1 Data
  • 1. Do not take with bile acid sequestrants. Administer drug at least 4 hours before or 4 hours after taking bile acid sequestrants, or at as great an interval as possible.

Interaksi Obat

467 Data
Aspartame The excretion of Seladelpar can be decreased when combined with Aspartame.
Pravastatin The excretion of Seladelpar can be decreased when combined with Pravastatin.
Pantoprazole The excretion of Seladelpar can be decreased when combined with Pantoprazole.
Cefotiam The excretion of Seladelpar can be decreased when combined with Cefotiam.
Liothyronine The excretion of Seladelpar can be decreased when combined with Liothyronine.
Conjugated estrogens The excretion of Seladelpar can be decreased when combined with Conjugated estrogens.
Valproic acid The excretion of Seladelpar can be decreased when combined with Valproic acid.
Indomethacin The excretion of Seladelpar can be decreased when combined with Indomethacin.
Aminohippuric acid The excretion of Seladelpar can be decreased when combined with Aminohippuric acid.
Lansoprazole The excretion of Seladelpar can be decreased when combined with Lansoprazole.
Cefalotin The excretion of Seladelpar can be decreased when combined with Cefalotin.
Tenoxicam The excretion of Seladelpar can be decreased when combined with Tenoxicam.
Cefotaxime The excretion of Seladelpar can be decreased when combined with Cefotaxime.
Zidovudine The excretion of Seladelpar can be decreased when combined with Zidovudine.
Cimetidine The excretion of Seladelpar can be decreased when combined with Cimetidine.
Guanidine The excretion of Seladelpar can be decreased when combined with Guanidine.
Piroxicam The excretion of Seladelpar can be decreased when combined with Piroxicam.
Methotrexate The excretion of Seladelpar can be decreased when combined with Methotrexate.
Cephalexin The excretion of Seladelpar can be decreased when combined with Cephalexin.
Enalapril The excretion of Seladelpar can be decreased when combined with Enalapril.
Diclofenac The excretion of Seladelpar can be decreased when combined with Diclofenac.
Oxytetracycline The excretion of Seladelpar can be decreased when combined with Oxytetracycline.
Linezolid The excretion of Seladelpar can be decreased when combined with Linezolid.
Leucovorin The excretion of Seladelpar can be decreased when combined with Leucovorin.
Latanoprost The excretion of Seladelpar can be decreased when combined with Latanoprost.
Furosemide The excretion of Seladelpar can be decreased when combined with Furosemide.
Esomeprazole The excretion of Seladelpar can be decreased when combined with Esomeprazole.
Tetracycline The excretion of Seladelpar can be decreased when combined with Tetracycline.
Acyclovir The excretion of Seladelpar can be decreased when combined with Acyclovir.
Phenylbutazone The excretion of Seladelpar can be decreased when combined with Phenylbutazone.
Cefaclor The excretion of Seladelpar can be decreased when combined with Cefaclor.
Bumetanide The excretion of Seladelpar can be decreased when combined with Bumetanide.
Quinidine The excretion of Seladelpar can be decreased when combined with Quinidine.
Dinoprostone The excretion of Seladelpar can be decreased when combined with Dinoprostone.
Famotidine The excretion of Seladelpar can be decreased when combined with Famotidine.
Salicylic acid The excretion of Seladelpar can be decreased when combined with Salicylic acid.
Acetylsalicylic acid The excretion of Seladelpar can be decreased when combined with Acetylsalicylic acid.
Ganciclovir The excretion of Seladelpar can be decreased when combined with Ganciclovir.
Ketoprofen The excretion of Seladelpar can be decreased when combined with Ketoprofen.
Minocycline The excretion of Seladelpar can be decreased when combined with Minocycline.
Probenecid The excretion of Seladelpar can be decreased when combined with Probenecid.
Mercaptopurine The excretion of Seladelpar can be decreased when combined with Mercaptopurine.
Ibuprofen The excretion of Seladelpar can be decreased when combined with Ibuprofen.
Novobiocin The excretion of Seladelpar can be decreased when combined with Novobiocin.
Benzylpenicillin The excretion of Seladelpar can be decreased when combined with Benzylpenicillin.
Melatonin The excretion of Seladelpar can be decreased when combined with Melatonin.
Ouabain The excretion of Seladelpar can be decreased when combined with Ouabain.
Rosuvastatin The excretion of Seladelpar can be decreased when combined with Rosuvastatin.
Cefadroxil The excretion of Seladelpar can be decreased when combined with Cefadroxil.
Ceftriaxone The excretion of Seladelpar can be decreased when combined with Ceftriaxone.
Gemfibrozil The excretion of Seladelpar can be decreased when combined with Gemfibrozil.
Cefamandole The excretion of Seladelpar can be decreased when combined with Cefamandole.
Cefazolin The excretion of Seladelpar can be decreased when combined with Cefazolin.
Cefoperazone The excretion of Seladelpar can be decreased when combined with Cefoperazone.
Ceftizoxime The excretion of Seladelpar can be decreased when combined with Ceftizoxime.
Cefacetrile The excretion of Seladelpar can be decreased when combined with Cefacetrile.
Ceftibuten The excretion of Seladelpar can be decreased when combined with Ceftibuten.
Liotrix The excretion of Seladelpar can be decreased when combined with Liotrix.
Cilastatin The excretion of Seladelpar can be decreased when combined with Cilastatin.
Tazobactam The excretion of Seladelpar can be decreased when combined with Tazobactam.
trans-2-hydroxycinnamic acid The excretion of Seladelpar can be decreased when combined with trans-2-hydroxycinnamic acid.
Topiroxostat The excretion of Seladelpar can be decreased when combined with Topiroxostat.
Cholic Acid The excretion of Seladelpar can be decreased when combined with Cholic Acid.
Glutaric Acid The excretion of Seladelpar can be decreased when combined with Glutaric Acid.
Benzoic acid The excretion of Seladelpar can be decreased when combined with Benzoic acid.
Taurocholic acid The excretion of Seladelpar can be decreased when combined with Taurocholic acid.
Caprylic acid The excretion of Seladelpar can be decreased when combined with Caprylic acid.
Dronedarone The excretion of Seladelpar can be decreased when combined with Dronedarone.
Ataluren The excretion of Seladelpar can be decreased when combined with Ataluren.
Teriflunomide The excretion of Seladelpar can be decreased when combined with Teriflunomide.
Dabrafenib The excretion of Seladelpar can be decreased when combined with Dabrafenib.
Dolutegravir The excretion of Seladelpar can be decreased when combined with Dolutegravir.
Cefaloridine The excretion of Seladelpar can be decreased when combined with Cefaloridine.
Lenvatinib The excretion of Seladelpar can be decreased when combined with Lenvatinib.
Tafamidis The excretion of Seladelpar can be decreased when combined with Tafamidis.
Encorafenib The excretion of Seladelpar can be decreased when combined with Encorafenib.
Cabotegravir The excretion of Seladelpar can be decreased when combined with Cabotegravir.
Apalutamide The excretion of Seladelpar can be decreased when combined with Apalutamide.
Capivasertib The excretion of Seladelpar can be decreased when combined with Capivasertib.
Vadadustat The excretion of Seladelpar can be decreased when combined with Vadadustat.
Fexinidazole The excretion of Seladelpar can be decreased when combined with Fexinidazole.
Favipiravir The excretion of Seladelpar can be decreased when combined with Favipiravir.
Pradigastat The excretion of Seladelpar can be decreased when combined with Pradigastat.
Enasidenib The excretion of Seladelpar can be decreased when combined with Enasidenib.
Fluconazole The metabolism of Seladelpar can be decreased when combined with Fluconazole.
Floxuridine The metabolism of Seladelpar can be decreased when combined with Floxuridine.
Nicardipine The metabolism of Seladelpar can be decreased when combined with Nicardipine.
Delavirdine The metabolism of Seladelpar can be decreased when combined with Delavirdine.
Capecitabine The metabolism of Seladelpar can be decreased when combined with Capecitabine.
Miconazole The metabolism of Seladelpar can be decreased when combined with Miconazole.
Sulfaphenazole The metabolism of Seladelpar can be decreased when combined with Sulfaphenazole.
Tepotinib The metabolism of Seladelpar can be decreased when combined with Tepotinib.
Rifampin The metabolism of Seladelpar can be decreased when combined with Rifampin.
Cyclosporine The metabolism of Seladelpar can be decreased when combined with Cyclosporine.
Caffeine The metabolism of Seladelpar can be decreased when combined with Caffeine.
Nelfinavir The metabolism of Seladelpar can be decreased when combined with Nelfinavir.
Diethylstilbestrol The metabolism of Seladelpar can be decreased when combined with Diethylstilbestrol.
Gefitinib The metabolism of Seladelpar can be decreased when combined with Gefitinib.
Beclomethasone dipropionate The metabolism of Seladelpar can be decreased when combined with Beclomethasone dipropionate.
Progesterone The metabolism of Seladelpar can be decreased when combined with Progesterone.

Target Protein

Peroxisome proliferator-activated receptor delta PPARD

Referensi & Sumber

Artikel (PubMed)
  • PMID: 35605662
    Kouno T, Liu X, Zhao H, Kisseleva T, Cable EE, Schnabl B: Selective PPARdelta agonist seladelpar suppresses bile acid synthesis by reducing hepatocyte CYP7A1 via the fibroblast growth factor 21 signaling pathway. J Biol Chem. 2022 Jul;298(7):102056. doi: 10.1016/j.jbc.2022.102056. Epub 2022 May 20.
  • PMID: 19636418
    Li T, Chiang JY: Regulation of bile acid and cholesterol metabolism by PPARs. PPAR Res. 2009;2009:501739. doi: 10.1155/2009/501739. Epub 2009 Jul 14.
  • PMID: 29083622
    Lowe D, Sanvictores T, Zubair M, John S: Alkaline Phosphatase. .
  • PMID: 38381664
    Hirschfield GM, Bowlus CL, Mayo MJ, Kremer AE, Vierling JM, Kowdley KV, Levy C, Villamil A, Ladron de Guevara Cetina AL, Janczewska E, Zigmond E, Jeong SH, Yilmaz Y, Kallis Y, Corpechot C, Buggisch P, Invernizzi P, Londono Hurtado MC, Bergheanu S, Yang K, Choi YJ, Crittenden DB, McWherter CA: A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis. N Engl J Med. 2024 Feb 29;390(9):783-794. doi: 10.1056/NEJMoa2312100. Epub 2024 Feb 21.

Contoh Produk & Brand

Produk: 1 • International brands: 0
Produk
  • Livdelzi
    Capsule • 10 mg/1 • Oral • US • Approved

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