Peringatan Keamanan

Overdosage with pacritinib may lead to gastrointestinal toxicity, myelosuppression, blurred vision, dizziness, worsening performance status, and sepsis.L40754 There is no known antidote for pacritinib overdose, and hemodialysis is not expected to enhance its elimination.L40754

Pacritinib

DB11697

small molecule approved investigational

Deskripsi

Myelofibrosis (MF) is a rare disorder characterized by hematopoietic abnormalities and fibrosis within the bone marrow.L40793 The underlying cause of primary MF is unknown, but secondary MF can arise in patients with a history of polycythemia vera or essential thrombocythemia.L40793 While some patients may remain asymptomatic, typical symptoms of MF arise from abnormalities in blood cell production and may therefore include various cytopenias, infections, splenomegaly, and general systemic symptoms such as fever.L40793 Approximately 50% of patients with primary MF have a mutation of the JAK2 gene, which is also commonly mutated in patients with polycythemia vera or essential thrombocythemia.L40793 JAK2 signaling is important for hematopoiesis and proper immune functioning,L40754 and while the precise role it plays in the pathogenesis of MF remains unclear, its clear association with MF has made it a desirable therapeutic target in MF treatment.

Pacritinib is an inhibitor of both wild-type and mutant (V617F) JAK2, as well as FMS-like tyrosine kinase 3 (FLT3), which was granted accelerated approval by the FDA in February 2022 for the treatment of both primary and secondary MF in patients with platelet counts < 50 x 109/L.L40754 It provides a treatment option for patients who have MF with severe thrombocytopenia, which occurs in approximately one-third of MF patients and carries with it a particularly poor prognosis.L40709

Struktur Molekul 2D

Berat 472.589
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) The mean effective half-life of pacritinib is 27.7 hours.[L40754]
Volume Distribusi The mean apparent volume of distribution of pacritinib at steady-state is 229 L.[L40754]
Klirens (Clearance) The mean apparent clearance of pacritinib is 2.09 L/h.[L40754]

Absorpsi

Following oral administration of 200mg pacritinib twice daily, the mean Cmax and AUC0-12 at steady-state were 8.4 mg/L and 95.6 mg*h/L, respectively.L40754 The Tmax is approximately 4-5 hours post-dose.L40754 Co-administration with food does not significantly impact the pharmacokinetics of pacritinib.

Metabolisme

Pacritinib metabolism is mediated primarily by CYP3A4.L40754 While it undergoes extensive metabolism to at least four identified metabolites - M1, M2, M3, and M4A245863 - parent drug is the major circulating component in plasma and is responsible for the pharmacologic activity.L40754 The two major metabolites, M1 and M2, represent 9.6% and 10.5% of parent drug exposure, respectively.L40754

Rute Eliminasi

Following oral administration of radiolabeled pacritinib, approximately 87% of the radioactivity was recovered in feces and 6% was recovered in urine.L40754 Unchanged parent drug was not present in the feces and accounted for only 0.12% of the radioactivity excreted in the urine.L40754

Interaksi Makanan

2 Data
  • 1. Avoid grapefruit products. Grapefruit products can inhibit CYP3A4, which is the enzyme primarily responsible for pacritinib metabolism.
  • 2. Avoid St. John's Wort. Pacritinib is metabolized primarily by CYP3A4, an enzyme for which St. John's wort is a potent inducer.

Interaksi Obat

855 Data
Acetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Pacritinib.
Propacetamol The serum concentration of Propacetamol can be increased when it is combined with Pacritinib.
Salmon calcitonin The therapeutic efficacy of Salmon calcitonin can be decreased when used in combination with Pacritinib.
Thyrotropin alfa The therapeutic efficacy of Thyrotropin alfa can be decreased when used in combination with Pacritinib.
Follitropin The therapeutic efficacy of Follitropin can be decreased when used in combination with Pacritinib.
Liothyronine The therapeutic efficacy of Liothyronine can be decreased when used in combination with Pacritinib.
Carbimazole The therapeutic efficacy of Carbimazole can be decreased when used in combination with Pacritinib.
Levothyroxine The therapeutic efficacy of Levothyroxine can be decreased when used in combination with Pacritinib.
Propylthiouracil The therapeutic efficacy of Propylthiouracil can be decreased when used in combination with Pacritinib.
Methimazole The serum concentration of Pacritinib can be increased when it is combined with Methimazole.
Liotrix The therapeutic efficacy of Liotrix can be decreased when used in combination with Pacritinib.
3,5-Diiodotyrosine The therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Pacritinib.
Tiratricol The therapeutic efficacy of Tiratricol can be decreased when used in combination with Pacritinib.
Parathyroid hormone The therapeutic efficacy of Parathyroid hormone can be decreased when used in combination with Pacritinib.
Teriparatide The therapeutic efficacy of Teriparatide can be decreased when used in combination with Pacritinib.
Potassium Iodide The therapeutic efficacy of Potassium Iodide can be decreased when used in combination with Pacritinib.
Dibromotyrosine The therapeutic efficacy of Dibromotyrosine can be decreased when used in combination with Pacritinib.
Thyroid, porcine The therapeutic efficacy of Thyroid, porcine can be decreased when used in combination with Pacritinib.
Potassium perchlorate The therapeutic efficacy of Potassium perchlorate can be decreased when used in combination with Pacritinib.
Protirelin The therapeutic efficacy of Protirelin can be decreased when used in combination with Pacritinib.
3,5-diiodothyropropionic acid The therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Pacritinib.
Methylthiouracil The therapeutic efficacy of Methylthiouracil can be decreased when used in combination with Pacritinib.
Elcatonin The therapeutic efficacy of Elcatonin can be decreased when used in combination with Pacritinib.
Benzylthiouracil The therapeutic efficacy of Benzylthiouracil can be decreased when used in combination with Pacritinib.
Thyrotropin The therapeutic efficacy of Thyrotropin can be decreased when used in combination with Pacritinib.
Leuprolide The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Leuprolide.
Goserelin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Goserelin.
Erythromycin The serum concentration of Pacritinib can be increased when it is combined with Erythromycin.
Azithromycin The metabolism of Azithromycin can be decreased when combined with Pacritinib.
Moxifloxacin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Moxifloxacin.
Ranolazine The serum concentration of Ranolazine can be increased when it is combined with Pacritinib.
Sulfisoxazole The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Sulfisoxazole.
Amitriptyline The metabolism of Amitriptyline can be decreased when combined with Pacritinib.
Methadone The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Methadone.
Diltiazem The serum concentration of Pacritinib can be increased when it is combined with Diltiazem.
Clozapine The serum concentration of Pacritinib can be increased when it is combined with Clozapine.
Sulpiride The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Sulpiride.
Nimodipine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Nimodipine.
Promazine The metabolism of Promazine can be decreased when combined with Pacritinib.
Prochlorperazine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Prochlorperazine.
Droperidol The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Droperidol.
Imipramine The serum concentration of Imipramine can be increased when it is combined with Pacritinib.
Chlorpromazine The metabolism of Chlorpromazine can be decreased when combined with Pacritinib.
Haloperidol The serum concentration of Pacritinib can be increased when it is combined with Haloperidol.
Oxaliplatin The serum concentration of Oxaliplatin can be increased when it is combined with Pacritinib.
Ciprofloxacin The serum concentration of Pacritinib can be increased when it is combined with Ciprofloxacin.
Fluorouracil The serum concentration of Fluorouracil can be increased when it is combined with Pacritinib.
Perflutren The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Perflutren.
Cinnarizine The metabolism of Cinnarizine can be decreased when combined with Pacritinib.
Atropine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Atropine.
Chloroquine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Chloroquine.
Efavirenz The serum concentration of Pacritinib can be increased when it is combined with Efavirenz.
Adenosine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Adenosine.
Pentamidine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Pentamidine.
Gadobenic acid The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Gadobenic acid.
Carbinoxamine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Carbinoxamine.
Dolasetron The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Dolasetron.
Roxithromycin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Roxithromycin.
Nalidixic acid The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Nalidixic acid.
Cinoxacin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Cinoxacin.
Loperamide The excretion of Loperamide can be decreased when combined with Pacritinib.
Granisetron The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Granisetron.
Ondansetron The metabolism of Ondansetron can be decreased when combined with Pacritinib.
Levosimendan The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Levosimendan.
Mesoridazine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Mesoridazine.
Desloratadine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Desloratadine.
Telithromycin The serum concentration of Pacritinib can be increased when it is combined with Telithromycin.
Lomefloxacin The metabolism of Lomefloxacin can be decreased when combined with Pacritinib.
Dimenhydrinate The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Dimenhydrinate.
Emedastine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Emedastine.
Primaquine The serum concentration of Pacritinib can be increased when it is combined with Primaquine.
Papaverine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Papaverine.
Chlorpheniramine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Chlorpheniramine.
Nifedipine The metabolism of Nifedipine can be decreased when combined with Pacritinib.
Levofloxacin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Levofloxacin.
Gemifloxacin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Gemifloxacin.
Ofloxacin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Ofloxacin.
Propafenone The metabolism of Propafenone can be decreased when combined with Pacritinib.
Flecainide The metabolism of Flecainide can be decreased when combined with Pacritinib.
Clarithromycin The serum concentration of Pacritinib can be increased when it is combined with Clarithromycin.
Quetiapine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Quetiapine.
Levacetylmethadol The serum concentration of Levacetylmethadol can be increased when it is combined with Pacritinib.
Saquinavir The serum concentration of Pacritinib can be increased when it is combined with Saquinavir.
Clomipramine The serum concentration of Clomipramine can be increased when it is combined with Pacritinib.
Mibefradil The serum concentration of Mibefradil can be increased when it is combined with Pacritinib.
Probucol The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Probucol.
Aceprometazine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Aceprometazine.
Terlipressin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Terlipressin.
Prenylamine The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Prenylamine.
Fluspirilene The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Fluspirilene.
Lofexidine The metabolism of Lofexidine can be decreased when combined with Pacritinib.
Azimilide The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Azimilide.
Pracinostat The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Pracinostat.
Technetium Tc-99m ciprofloxacin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Technetium Tc-99m ciprofloxacin.
Garenoxacin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Garenoxacin.
Tedisamil The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Tedisamil.
Tucidinostat The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Tucidinostat.
Telavancin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Telavancin.
Pazopanib The serum concentration of Pazopanib can be increased when it is combined with Pacritinib.
Nemonoxacin The risk or severity of QTc prolongation can be increased when Pacritinib is combined with Nemonoxacin.

Target Protein

Tyrosine-protein kinase JAK3 JAK3
Tyrosine-protein kinase JAK2 JAK2
Receptor-type tyrosine-protein kinase FLT3 FLT3

Referensi & Sumber

Synthesis reference: A245943 — William AD, Lee AC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Tan E, Chen D, Williams M, Sun ET, Goh KC, Ong WC, Goh SK, Hart S, Jayaraman R, Pasha MK, Ethirajulu K, Wood JM, Dymock BW: Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo19.3.1.1(2,6). 1(8,12)heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J Med Chem. 2011 Jul 14;54(13):4638-58. doi: 10.1021/jm200326p. Epub 2011 Jun 15.
Artikel (PubMed)
  • PMID: 25600203
    Jayaraman R, Pasha MK, Williams A, Goh KC, Ethirajulu K: Metabolism and Disposition of Pacritinib (SB1518), an Orally Active Janus Kinase 2 Inhibitor in Preclinical Species and Humans. Drug Metab Lett. 2015;9(1):28-47. doi: 10.2174/1872312809666150119105250.

Contoh Produk & Brand

Produk: 1 • International brands: 0
Produk
  • Vonjo
    Capsule • 100 mg/1 • Oral • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.
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