Peringatan Keamanan

No pegloticase overdose cases have been reported. The single maximum intravenous dose that has been administered is 12 mg as uricase protein.^L42425 Patients experiencing an overdose are at an increased risk of severe adverse effects such as anaphylaxis, gout flares and congestive heart failure. The drug label recommends to monitor patients suspected of experiencing a pegloticase overdose, and initiate general supportive measures as no specific antidote has been identified.^L42425

The carcinogenic and genotoxic potential of pegloticase has not been evaluated. At doses up to 40 mg/kg, pegloticase did not show evidence of fertility impairment in rats (dose equivalent to 50 times the maximum recommended human dose.^L42425

Pegloticase

DB09208

biotech approved investigational

Deskripsi

Pegloticase is a porcine recombinant PEGylated uricase indicated for the treatment of chronic gout in adult patients that do not respond to other types of therapies.^L42425 Pegloticase has a similar activity to rasburicase, an enzyme that metabolizes uric acid to allantoin. In gout patients treated with pegloticase, the conversion of uric acid to allantoin leads to lower plasma uric acid concentrations.^L42425

Pegloticase has a longer terminal elimination half-life thanks to the addition of a polyethylene glycol (PEG) group. Therefore therapeutic drug levels can be maintained with infrequent and relatively low pegloticase doses.^A249980 The PEG group also gives pegloticase a lower potential to induce an immune response.^A249980 However, cases of anaphylaxis and infusion reactions have been reported in patients treated with this drug.^L42425 Pegloticase was approved by the FDA in 2014, and in 2022, the drug label included the co-administration of pegloticase and methotrexate.^L42425

Struktur Molekul 2D

Struktur tidak tersedia

Peta Jejaring Molekuler

Obat Target Gen Interaksi Enzim Transporter Carrier

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

1. Pendahuluan & Konsep

Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).

2. Sumber Data (Validasi)

Data Obat: Diekstraksi dari elemen drugbank-id dan name pada skema XML DrugBank.
Target Protein: Diambil dari elemen targets/target yang memuat polipeptida sasaran.
Genetik: Disinkronisasi dari sub-elemen gene-name dan varian snp-effects.
Genetik: Jumlah titik node dibatasi pada maksimal 10 (Slice=10) interaksi untuk menghindari tumpukan data.

3. Algoritma Visualisasi

Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.

4. Legenda Visual

Obat Utama (Pusat Analisis)

Target Protein (Mekanisme)

Gen (Faktor Genetik)

Metode ini mendukung analisis Precision Medicine dan evaluasi risiko Drug-Drug Interaction (DDI).

Profil Farmakokinetik

Waktu Paruh (Half-Life) In patients with symptomatic gout given single-dose intravenous infusions of pegloticase (0.5 to 12 mg), half-life ranged from 6.4 to 13.8 days. The mean plasma half-life of pegloticase was 300 hr or 12.5 days.[A249975] In a second study where gout patients were given 4 to 12 mg of pegloticase intravenously every 2 or 4 weeks, the mean terminal elimination half-life of pegloticase in serum was approximately 2 weeks long, ranging from 170 to 1049 hours.[A249980]

Volume Distribusi The volume of distribution of pegloticase ranges from 5 to 10 L.[A249975]

Klirens (Clearance) In gout patients given 4 to 12 mg of pegloticase intravenously every 2 or 4 weeks, the mean clearance was ??0.0000854 L/h/kg.[A249980]

Absorpsi

In patients with symptomatic gout given single-dose intravenous infusions of pegloticase (0.5 to 12 mg), maximum serum concentrations of pegloticase increased in a dose proportional manner.^L42425 The AUC increased linearly up to a dose of 8 mg.^A249975 Pegloticase administered intravenously has a T_max of 2.25 h (range from 1.92 to 4.25 h), a C_max of 2.17 µg/ml (range from 1.25 to 4.77 µg/ml), and an AUC_0-t of 445 h?µg/ml (range from 223 to 1040 h?µg/ml).^L42430 Since pegloticase is administered intravenously, it is expected that it has a bioavailability close to 100%. The pharmacokinetic profile of pegloticase is not significantly influenced by age, sex, weight, and creatinine clearance; however, it is affected by body surface area and anti-pegloticase antibodies.^L42425

Metabolisme

As a recombinant enzyme, pegloticase is expected to be metabolized by proteases throughout the body.

Rute Eliminasi

Nonclinical studies suggest that pegloticase is renally excreted. Due to the PEG moiety pegloticase, urinary excretion is likely to be the primary route of elimination.^L42430

Interaksi Obat

58 Data

Febuxostat	The risk or severity of adverse effects can be increased when Febuxostat is combined with Pegloticase.
Peginterferon alfa-2a	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Peginterferon alfa-2a.
Pegfilgrastim	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Pegfilgrastim.
Peginterferon alfa-2b	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Peginterferon alfa-2b.
Pegaspargase	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Pegaspargase.
Pegademase	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Pegademase.
Pegvisomant	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Pegvisomant.
Propylene glycol	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Propylene glycol.
Heptaethylene glycol	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Heptaethylene glycol.
Pegaptanib	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Pegaptanib.
Egaptivon pegol	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Egaptivon pegol.
PEG-uricase	The therapeutic efficacy of Pegloticase can be decreased when used in combination with PEG-uricase.
Peginterferon alfacon-1	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Peginterferon alfacon-1.
GlycoPEG-GCSF	The therapeutic efficacy of Pegloticase can be decreased when used in combination with GlycoPEG-GCSF.
Pegnivacogin	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Pegnivacogin.
Pegpleranib	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Pegpleranib.
Pegsunercept	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Pegsunercept.
Polidocanol	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Polidocanol.
Peginesatide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Peginesatide.
Certolizumab pegol	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Certolizumab pegol.
Methoxy polyethylene glycol-epoetin beta	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Methoxy polyethylene glycol-epoetin beta.
Peginterferon beta-1a	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Peginterferon beta-1a.
Polyethylene glycol	The therapeutic efficacy of Polyethylene glycol can be decreased when used in combination with Pegloticase.
Antihemophilic factor (recombinant), PEGylated	The therapeutic efficacy of Antihemophilic factor (recombinant), PEGylated can be decreased when used in combination with Pegloticase.
Insulin peglispro	The therapeutic efficacy of Insulin peglispro can be decreased when used in combination with Pegloticase.
Eptacog alfa pegol (activated)	The therapeutic efficacy of Eptacog alfa pegol (activated) can be decreased when used in combination with Pegloticase.
Olaptesed Pegol	The therapeutic efficacy of Olaptesed Pegol can be decreased when used in combination with Pegloticase.
Abicipar Pegol	The therapeutic efficacy of Abicipar Pegol can be decreased when used in combination with Pegloticase.
Lexaptepid pegol	The therapeutic efficacy of Lexaptepid pegol can be decreased when used in combination with Pegloticase.
Cepeginterferon alfa-2B	The therapeutic efficacy of Cepeginterferon alfa-2B can be decreased when used in combination with Pegloticase.
Pegvaliase	The therapeutic efficacy of Pegvaliase can be decreased when used in combination with Pegloticase.
Pegamotecan	The therapeutic efficacy of Pegamotecan can be decreased when used in combination with Pegloticase.
Lipegfilgrastim	The therapeutic efficacy of Lipegfilgrastim can be decreased when used in combination with Pegloticase.
Nonacog beta pegol	The therapeutic efficacy of Nonacog beta pegol can be decreased when used in combination with Pegloticase.
Damoctocog alfa pegol	The therapeutic efficacy of Damoctocog alfa pegol can be decreased when used in combination with Pegloticase.
Elapegademase	The therapeutic efficacy of Elapegademase can be decreased when used in combination with Pegloticase.
Allopurinol	The risk or severity of adverse effects can be increased when Allopurinol is combined with Pegloticase.
Probenecid	The risk or severity of adverse effects can be increased when Probenecid is combined with Pegloticase.
Sulfinpyrazone	The risk or severity of adverse effects can be increased when Sulfinpyrazone is combined with Pegloticase.
Tienilic acid	The risk or severity of adverse effects can be increased when Tienilic acid is combined with Pegloticase.
Azapropazone	The risk or severity of adverse effects can be increased when Azapropazone is combined with Pegloticase.
Lesinurad	The risk or severity of adverse effects can be increased when Lesinurad is combined with Pegloticase.
Benzbromarone	The risk or severity of adverse effects can be increased when Benzbromarone is combined with Pegloticase.
Benziodarone	The risk or severity of adverse effects can be increased when Benziodarone is combined with Pegloticase.
Methyclothiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Methyclothiazide.
Bendroflumethiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Bendroflumethiazide.
Benzthiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Benzthiazide.
Cyclothiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Cyclothiazide.
Hydroflumethiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Hydroflumethiazide.
Chlorothiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Chlorothiazide.
Hydrochlorothiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Hydrochlorothiazide.
Trichlormethiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Trichlormethiazide.
Polythiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Polythiazide.
Mebutizide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Mebutizide.
Cyclopenthiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Cyclopenthiazide.
Buthiazide	The therapeutic efficacy of Pegloticase can be decreased when used in combination with Buthiazide.
Rurioctocog alfa pegol	The therapeutic efficacy of Rurioctocog alfa pegol can be decreased when used in combination with Pegloticase.
Methotrexate	The serum concentration of Pegloticase can be increased when it is combined with Methotrexate.

Target Protein

Uric acid

Referensi & Sumber

Synthesis reference: Hartman, J., et al. (2006). Variant form of urate oxidase and use thereof (U.S. Patent No. 8,293,228 B2). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/30/f1/72/f63e5683fed87b/US8293228.pdf

Artikel (PubMed)

PMID: 27493693
Sattui SE, Gaffo AL: Treatment of hyperuricemia in gout: current therapeutic options, latest developments and clinical implications. Ther Adv Musculoskelet Dis. 2016 Aug;8(4):145-59. doi: 10.1177/1759720X16646703. Epub 2016 May 2.
PMID: 17328081
Sundy JS, Ganson NJ, Kelly SJ, Scarlett EL, Rehrig CD, Huang W, Hershfield MS: Pharmacokinetics and pharmacodynamics of intravenous PEGylated recombinant mammalian urate oxidase in patients with refractory gout. Arthritis Rheum. 2007 Mar;56(3):1021-8. doi: 10.1002/art.22403.
PMID: 18420531
Yue CS, Huang W, Alton M, Maroli AN, Waltrip RW, Wright D, Marco MD: Population pharmacokinetic and pharmacodynamic analysis of pegloticase in subjects with hyperuricemia and treatment-failure gout. J Clin Pharmacol. 2008 Jun;48(6):708-18. doi: 10.1177/0091270008317589. Epub 2008 Apr 16.
PMID: 22395256
Shannon JA, Cole SW: Pegloticase: a novel agent for treatment-refractory gout. Ann Pharmacother. 2012 Mar;46(3):368-76. doi: 10.1345/aph.1Q593. Epub 2012 Mar 6.

Link

Contoh Produk & Brand

Produk: 4 • International brands: 0

Produk

Krystexxa

Injection, solution • 8 mg/1mL • Intravenous • US • Approved
Krystexxa

Injection, solution, concentrate • 8 mg/ml • Intravenous • EU
Krystexxa

Injection, solution • 8 mg/1mL • Intravenous • US • Approved
Krystexxa

Injection, solution • 8 mg/1mL • Intravenous • US • Approved

Sekuens Gen/Protein (FASTA)

Sekuens dimuat saat dibutuhkan agar halaman tetap ringan.