Peringatan Keamanan

There is no clinical experience with brincidofovir overdose. Patients experiencing overdosage should be monitored closely and provided supportive therapy as clinically indicated.L34404

Brincidofovir

DB12151

small molecule approved investigational

Deskripsi

Brincidofovir is an oral antiviral drug used in the treatment of human smallpox infections. It is a lipid conjugate pro-drug of the acyclic nucleotide analogue cidofovirL34404,A235725 - this lipid conjugate improves drug delivery to the target cells and significantly reduces the nephrotoxicity typically associated with cidofovir therapy.A235725,A235735 Due to its formulation as a pro-drug brincidofovir also carries a greater bioavailability than cidofovir,A235740,A235725 allowing for oral administration rather than intravenous. Cidofovir itself has broad antiviral activity against several DNA viruses,A235725 resulting in brincidofovir being investigated for the prevention and treatment of cytomegalovirus (CMV), BK Virus (BKV), adenoviruses (AdV), and Epstein-Barr virus (EBV), amongst others.

Brincidofovir, developed by Chimerix under the brand name Tembexa, was approved by the FDA for the treatment of smallpox infection in June 2021.L34470 As smallpox has been eradicated, the efficacy of Tembexa was assessed in animals infected with viruses closely related to variola. The approval was granted under the agency’s Animal Rule,L34480 which allows for a drug to be approved based on the results of well-controlled animal studies when human trials would be unethical or infeasible.

Struktur Molekul 2D

Berat 561.701
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 terminal half-lives of brincidofovir and its pharmacologically active metabolite, cidofovir diphosphate, are 19.3 hours and 113 hours, respectively.[L34404]
Volume Distribusi The apparent volume of distribution of brincidofovir is 1230 L.[L34404]
Klirens (Clearance) The apparent clearance of brincidofovir in healthy adult patients is 44.1 L/h.[L34404]

Absorpsi

The oral bioavailability of brincidofovir is 13.4% in its tablet formulation and 16.8% in its suspension formulation.L34404 Following oral administration, the Cmax and AUCtau of brincidofovir were 480 ng/mL and 3400 ng·hr/mL, respectively. The Cmax and AUCtau of the active metabolite, cidofovir diphosphate, were 9.7 pg/106 cells and 1200 pg·hr/106 cells, respectively.L34404 Maximum plasma concentrations (Tmax) of brincidofovir are reached at approximately 3 hours post-administration, while maximal plasma concentrations for cidofovir diphosphate are reached at approximately 47 hours post-administration.L34404

Metabolisme

Brincidofovir is a pro-drug of cidofovir and as such must undergo some basic metabolic reactions to become pharmacologically active. Upon entering the target cell, the phosphodiester bond of brincidofovir is hydrolyzed to generate cidofovir, which is then phosphorylated to generate the active agent: cidofovir diphosphate.L34404 The specific enzyme(s) responsible for this reaction have not been elucidated, but in vitro findings suggest sphingomyelin phosphodiesterase plays a major role in the initial hydrolysis of brincidofovir.L34404 There are two major inactive metabolites of brincidofovir, CMX103 and CMX064, which are generated via carboxylation of the terminal carbon followed by several cycles of CYP-mediated oxidative reactions and fatty acid oxidation.L34404,A235735 These reactions are mediated, at least in part, by CYP4F2.L34404

Rute Eliminasi

Brincidofovir is eliminated as metabolites in both the urine (~51%) and feces (~40%).L34404

Interaksi Makanan

1 Data
  • 1. Take on an empty stomach. Brincidofovir is best absorbed on an empty stomach or alongside a low-fat meal.

Interaksi Obat

143 Data
Apalutamide The serum concentration of Brincidofovir can be decreased when it is combined with Apalutamide.
Filgotinib The serum concentration of Brincidofovir can be increased when it is combined with Filgotinib.
Digoxin The serum concentration of Brincidofovir can be increased when it is combined with Digoxin.
Quinidine The serum concentration of Brincidofovir can be increased when it is combined with Quinidine.
Cyclosporine The serum concentration of Brincidofovir can be increased when it is combined with Cyclosporine.
Indomethacin The serum concentration of Brincidofovir can be increased when it is combined with Indomethacin.
Diclofenac The serum concentration of Brincidofovir can be increased when it is combined with Diclofenac.
Sulfasalazine The serum concentration of Brincidofovir can be increased when it is combined with Sulfasalazine.
Tacrolimus The serum concentration of Brincidofovir can be increased when it is combined with Tacrolimus.
Atazanavir The serum concentration of Brincidofovir can be increased when it is combined with Atazanavir.
Lopinavir The serum concentration of Brincidofovir can be increased when it is combined with Lopinavir.
Reserpine The serum concentration of Brincidofovir can be increased when it is combined with Reserpine.
Pantoprazole The serum concentration of Brincidofovir can be increased when it is combined with Pantoprazole.
Conjugated estrogens The serum concentration of Brincidofovir can be increased when it is combined with Conjugated estrogens.
Rosiglitazone The serum concentration of Brincidofovir can be increased when it is combined with Rosiglitazone.
Levocarnitine The serum concentration of Brincidofovir can be increased when it is combined with Levocarnitine.
Estradiol The serum concentration of Brincidofovir can be increased when it is combined with Estradiol.
Gemfibrozil The serum concentration of Brincidofovir can be increased when it is combined with Gemfibrozil.
Sacubitril The serum concentration of Brincidofovir can be increased when it is combined with Sacubitril.
Estradiol acetate The serum concentration of Brincidofovir can be increased when it is combined with Estradiol acetate.
Estradiol cypionate The serum concentration of Brincidofovir can be increased when it is combined with Estradiol cypionate.
Estradiol dienanthate The serum concentration of Brincidofovir can be increased when it is combined with Estradiol dienanthate.
Estradiol valerate The serum concentration of Brincidofovir can be increased when it is combined with Estradiol valerate.
Valsartan The serum concentration of Brincidofovir can be increased when it is combined with Valsartan.
Troglitazone The serum concentration of Brincidofovir can be increased when it is combined with Troglitazone.
Erythromycin The serum concentration of Brincidofovir can be increased when it is combined with Erythromycin.
Sildenafil The serum concentration of Brincidofovir can be increased when it is combined with Sildenafil.
Nelfinavir The serum concentration of Brincidofovir can be increased when it is combined with Nelfinavir.
Indinavir The serum concentration of Brincidofovir can be increased when it is combined with Indinavir.
Diethylstilbestrol The serum concentration of Brincidofovir can be increased when it is combined with Diethylstilbestrol.
Beclomethasone dipropionate The serum concentration of Brincidofovir can be increased when it is combined with Beclomethasone dipropionate.
Progesterone The serum concentration of Brincidofovir can be increased when it is combined with Progesterone.
Cerivastatin The serum concentration of Brincidofovir can be increased when it is combined with Cerivastatin.
Quinine The serum concentration of Brincidofovir can be increased when it is combined with Quinine.
Ritonavir The serum concentration of Brincidofovir can be increased when it is combined with Ritonavir.
Caspofungin The serum concentration of Brincidofovir can be increased when it is combined with Caspofungin.
Vincristine The serum concentration of Brincidofovir can be increased when it is combined with Vincristine.
Vinblastine The serum concentration of Brincidofovir can be increased when it is combined with Vinblastine.
Fluticasone propionate The serum concentration of Brincidofovir can be increased when it is combined with Fluticasone propionate.
Ivermectin The serum concentration of Brincidofovir can be increased when it is combined with Ivermectin.
Nicardipine The serum concentration of Brincidofovir can be increased when it is combined with Nicardipine.
Simvastatin The serum concentration of Brincidofovir can be increased when it is combined with Simvastatin.
Nystatin The serum concentration of Brincidofovir can be increased when it is combined with Nystatin.
Estrone The serum concentration of Brincidofovir can be increased when it is combined with Estrone.
Amprenavir The serum concentration of Brincidofovir can be increased when it is combined with Amprenavir.
Irinotecan The serum concentration of Brincidofovir can be increased when it is combined with Irinotecan.
Roxithromycin The serum concentration of Brincidofovir can be increased when it is combined with Roxithromycin.
Mifepristone The serum concentration of Brincidofovir can be increased when it is combined with Mifepristone.
Sirolimus The serum concentration of Brincidofovir can be increased when it is combined with Sirolimus.
Tipranavir The serum concentration of Brincidofovir can be increased when it is combined with Tipranavir.
Dipyridamole The serum concentration of Brincidofovir can be increased when it is combined with Dipyridamole.
Telithromycin The serum concentration of Brincidofovir can be increased when it is combined with Telithromycin.
Ketoconazole The serum concentration of Brincidofovir can be increased when it is combined with Ketoconazole.
Novobiocin The serum concentration of Brincidofovir can be increased when it is combined with Novobiocin.
Atorvastatin The serum concentration of Brincidofovir can be increased when it is combined with Atorvastatin.
Ouabain The serum concentration of Brincidofovir can be increased when it is combined with Ouabain.
Fluvastatin The serum concentration of Brincidofovir can be increased when it is combined with Fluvastatin.
Rosuvastatin The serum concentration of Brincidofovir can be increased when it is combined with Rosuvastatin.
Clarithromycin The serum concentration of Brincidofovir can be increased when it is combined with Clarithromycin.
Saquinavir The serum concentration of Brincidofovir can be increased when it is combined with Saquinavir.
Darunavir The serum concentration of Brincidofovir can be increased when it is combined with Darunavir.
Bezafibrate The serum concentration of Brincidofovir can be increased when it is combined with Bezafibrate.
Everolimus The serum concentration of Brincidofovir can be increased when it is combined with Everolimus.
Genistein The serum concentration of Brincidofovir can be increased when it is combined with Genistein.
Hyperforin The serum concentration of Brincidofovir can be increased when it is combined with Hyperforin.
Cholic Acid The serum concentration of Brincidofovir can be increased when it is combined with Cholic Acid.
Fusidic acid The serum concentration of Brincidofovir can be increased when it is combined with Fusidic acid.
Quercetin The serum concentration of Brincidofovir can be increased when it is combined with Quercetin.
Taurocholic acid The serum concentration of Brincidofovir can be increased when it is combined with Taurocholic acid.
Posizolid The serum concentration of Brincidofovir can be increased when it is combined with Posizolid.
Dronedarone The serum concentration of Brincidofovir can be increased when it is combined with Dronedarone.
Nilotinib The serum concentration of Brincidofovir can be increased when it is combined with Nilotinib.
Telaprevir The serum concentration of Brincidofovir can be increased when it is combined with Telaprevir.
Dovitinib The serum concentration of Brincidofovir can be increased when it is combined with Dovitinib.
Acetylcysteine The serum concentration of Brincidofovir can be increased when it is combined with Acetylcysteine.
Eltrombopag The serum concentration of Brincidofovir can be increased when it is combined with Eltrombopag.
Simeprevir The serum concentration of Brincidofovir can be increased when it is combined with Simeprevir.
Pazopanib The serum concentration of Brincidofovir can be increased when it is combined with Pazopanib.
Axitinib The serum concentration of Brincidofovir can be increased when it is combined with Axitinib.
Cholecystokinin The serum concentration of Brincidofovir can be increased when it is combined with Cholecystokinin.
Rilpivirine The serum concentration of Brincidofovir can be increased when it is combined with Rilpivirine.
Teriflunomide The serum concentration of Brincidofovir can be increased when it is combined with Teriflunomide.
Dabrafenib The serum concentration of Brincidofovir can be increased when it is combined with Dabrafenib.
Idelalisib The serum concentration of Brincidofovir can be increased when it is combined with Idelalisib.
Cobicistat The serum concentration of Brincidofovir can be increased when it is combined with Cobicistat.
Lenvatinib The serum concentration of Brincidofovir can be increased when it is combined with Lenvatinib.
Daclatasvir The serum concentration of Brincidofovir can be increased when it is combined with Daclatasvir.
Lobeglitazone The serum concentration of Brincidofovir can be increased when it is combined with Lobeglitazone.
Eluxadoline The serum concentration of Brincidofovir can be increased when it is combined with Eluxadoline.
Paritaprevir The serum concentration of Brincidofovir can be increased when it is combined with Paritaprevir.
Silibinin The serum concentration of Brincidofovir can be increased when it is combined with Silibinin.
Venetoclax The serum concentration of Brincidofovir can be increased when it is combined with Venetoclax.
Asunaprevir The serum concentration of Brincidofovir can be increased when it is combined with Asunaprevir.
Velpatasvir The serum concentration of Brincidofovir can be increased when it is combined with Velpatasvir.
Istradefylline The serum concentration of Brincidofovir can be increased when it is combined with Istradefylline.
Fostemsavir The serum concentration of Brincidofovir can be increased when it is combined with Fostemsavir.
Valspodar The serum concentration of Brincidofovir can be increased when it is combined with Valspodar.
Bempedoic acid The serum concentration of Brincidofovir can be increased when it is combined with Bempedoic acid.
Voxilaprevir The serum concentration of Brincidofovir can be increased when it is combined with Voxilaprevir.
Benzbromarone The serum concentration of Brincidofovir can be increased when it is combined with Benzbromarone.

Target Protein

DNA polymerase nu POLN
DNA polymerase delta subunit 4 POLD4
DNA polymerase delta catalytic subunit POLD1
DNA polymerase theta POLQ
DNA polymerase beta POLB
DNA polymerase subunit gamma-2 POLG2
DNA polymerase subunit gamma-1 POLG
DNA polymerase epsilon subunit 2 POLE2
DNA polymerase POL
Variola virus DNA

Referensi & Sumber

Synthesis reference: Hostetler KY: Synthesis and early development of hexadecyloxypropylcidofovir: an oral antipoxvirus nucleoside phosphonate. Viruses. 2010 Oct;2(10):2213-25. doi: 10.3390/v2102213. Epub 2010 Sep 30.
Artikel (PubMed)
  • PMID: 17724153
    Quenelle DC, Prichard MN, Keith KA, Hruby DE, Jordan R, Painter GR, Robertson A, Kern ER: Synergistic efficacy of the combination of ST-246 with CMX001 against orthopoxviruses. Antimicrob Agents Chemother. 2007 Nov;51(11):4118-24. Epub 2007 Aug 27.
  • PMID: 17904231
    Parker S, Touchette E, Oberle C, Almond M, Robertson A, Trost LC, Lampert B, Painter G, Buller RM: Efficacy of therapeutic intervention with an oral ether-lipid analogue of cidofovir (CMX001) in a lethal mousepox model. Antiviral Res. 2008 Jan;77(1):39-49. Epub 2007 Sep 4.
  • PMID: 31932370
    Delaune D, Iseni F: Drug Development against Smallpox: Present and Future. Antimicrob Agents Chemother. 2020 Mar 24;64(4). pii: AAC.01683-19. doi: 10.1128/AAC.01683-19. Print 2020 Mar 24.
  • PMID: 27851688
    Tippin TK, Morrison ME, Brundage TM, Mommeja-Marin H: Brincidofovir Is Not a Substrate for the Human Organic Anion Transporter 1: A Mechanistic Explanation for the Lack of Nephrotoxicity Observed in Clinical Studies. Ther Drug Monit. 2016 Dec;38(6):777-786. doi: 10.1097/FTD.0000000000000353.
  • PMID: 22391537
    Painter W, Robertson A, Trost LC, Godkin S, Lampert B, Painter G: First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses. Antimicrob Agents Chemother. 2012 May;56(5):2726-34. doi: 10.1128/AAC.05983-11. Epub 2012 Mar 5.
  • PMID: 21994617
    Hostetler KY: Synthesis and early development of hexadecyloxypropylcidofovir: an oral antipoxvirus nucleoside phosphonate. Viruses. 2010 Oct;2(10):2213-25. doi: 10.3390/v2102213. Epub 2010 Sep 30.

Contoh Produk & Brand

Produk: 6 • International brands: 1
Produk
  • Tembexa
    Tablet, film coated • 100 mg/1 • Oral • US • Approved
  • Tembexa
    Suspension • 10 mg/1mL • Oral • US • Approved
  • Tembexa
    Tablet • 100 mg • Oral • Canada • Approved
  • Tembexa
    Suspension • 10 mg / mL • Oral • Canada • Approved
  • Tembexa
    Tablet, film coated • 100 mg/1 • Oral • US • Approved
  • Tembexa
    Suspension • 10 mg/1mL • Oral • US • Approved
International Brands
  • Tembexa — Chimerix

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