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Baloxavir marboxil

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Baloxavir marboxil
Names
Trade namesXofluza
Other namesBXM (S-033188), BXA (S-033447)
Clinical data
Pregnancy
category
Routes of
use		By mouth
External links
AHFS/Drugs.comTempleeti:Drugs.com
MedlinePlusa618062
Legal
[[Regulation of therapeutic goods |Templeeti:Engvar data]]
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ATC code
Chemical and physical data
FormulaC27H23F2N3O7S
Molar massTempleeti:Val g·mol−1
3D model (JSmol)

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Baloxavirmarboxil structure formula v.1.svg

Baloxavir marboxil, nke a na-ere n'okpuru aha Xofluza, bụ ọgwụ na-egbochi nje maka ọgwụgwọ influenza A na influenza B. A kwadoro ya maka iji ya mee ihe na Japan na United States na 2018, a na-aṅụkwa ya dị ka otu ọgwụ site n'ọnụ.[4][7][8][4] Ọ nwere ike belata oge mgbaàmà nke influenza site na ihe dịka otu ụbọchị, mana ọ na-ahọrọ nhọrọ nke mutants na-eguzogide ya nke na-eme ka ọ ghara ịdị irè.[9]

E mepụtara Baloxavir marboxil dị ka usoro ọgwụ, na metabolism ya na-ahapụ ihe na-arụ ọrụ, baloxavir acid (BXA). Baloxavir acid na-arụ ọrụ dị ka enzyme inhibitor, na-elekwasị anya na ọrụ endonuclease nke na-adabere na cap influenza virus, nke a na-eji na "cap snatching" site na mgbagwoju anya polymerase virus, usoro dị mkpa maka ndụ ya.[10]

Mmetụta ndị a na-ahụkarị nke baloxavir marboxil gụnyere afọ ọsịsa, bronchitis, agbọ onunu, sinusitis, na isi ọwụwa.

US Food and Drug Administration (FDA) na-ewere baloxavir marboxil dị ka ọgwụ mbụ na klas.

Ojiji ọgwụ

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Baloxavir marboxil bụ ọgwụ influenza, ọgwụ na-egbochi nje, maka ndị mmadụ dị afọ iri na abụọ ma ọ bụ karịa, ndị gosipụtara mgbaàmà nke ọrịa a ruo ihe na-erughị awa 48.[11][4][5][11][5][11][12] Enwetabeghị ịdị irè nke baloxavir marboxil nyere mgbe awa 48 gasịrị.[11]

N'ọnwa Ọktoba 2019, FDA kwadoro ihe ngosi emelitere maka ọgwụgwọ nke influenza siri ike, nke na-enweghị mgbagwoju anya na ndị mmadụ dị afọ iri na abụọ ma ọ bụ karịa nọ n'ihe ize ndụ nke nsogbu influenza.[4][8]

N'ọnwa Nọvemba 2020, FDA kwadoro ihe ngosi emelitere iji tinye mgbochi mgbochi nke influenza (flu) maka ndị mmadụ dị afọ iri na abụọ ma ọ bụ karịa mgbe ha zutere onye nwere influenza.[4]

N'ọnwa Ọgọstụ 2022, FDA kwadoro ihe ngosi emelitere iji tinye mgbochi mgbochi nke influenza (flu) maka ndị mmadụ dị afọ ise ma ọ bụ karịa mgbe ha zutere onye nwere influenza.[4]

Na EU, a na-egosi baloxavir marboxil maka ọgwụgwọ nke influenza na-enweghị mgbagwoju anya na maka mgbochi mgbochi nke influenza na ndị mmadụ dị afọ iri na abụọ ma ọ bụ karịa.[5]

Ụdị ndị dịnụ

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Baloxavir marboxil dị n'ụdị mbadamba na dị ka granules maka ịgwakọta na mmiri.

Mmegide

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Na 2.2% nke ndị na-anata baloxavir na ule nke abụọ na ihe dị ka 10% nke ndị na na-anara baloxavir n'ule nke atọ, ụdị influenza na-ebute ọrịa enwetala nguzogide ọgwụ ahụ, n'ihi ụdị protein polymerase na-egosipụta mgbanwe nke isoleucine-38, kpọmkwem, I38T, I38M, ma ọ bụ I38F mutations.[13] A na-aga n'ihu na nchegbu na nchegbu ahụike banyere nguzogide na-apụta na ndị nnata, na nzaghachi maka ọgwụgwọ a.[14][15]

Ihe mgbochi

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E kwesịghị iji ngwaahịa mmiri ara ehi, ihe ọṅụṅụ calcium-fortified, ma ọ bụ laxatives, antacids, ma ọ bụrụ ihe mgbakwunye ọnụ nwere calcium, iron, magnesium, selenium, aluminum ma ọ bụ zinc.

Mmetụta ndị ọzọ

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Mmetụta ndị na-adịghị mma na-esote otu ọgwụgwọ nke baloxavir marboxil gụnyere afọ ọsịsa, bronchitis, oyi, isi ọwụwa, na agbọ onunu.[4][12] A kọrọ ihe ọjọọ na 21% nke ndị natara baloxavir, 25% nke ndị natarịrị placebo, na 25% nke oseltamivir.[13]

Usoro nke ọrụ

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Baloxavir marboxil bụ ihe na-agwọ ọrịa influenza, ọkachasị, ihe na-egbochi enzyme nke na-elekwasị anya na ọrụ endonuclease nke na-adabere na nje influenza, otu n'ime ọrụ nke nje polymerase complex.[16] Karịsịa, ọ na-egbochi usoro a maara dị ka cap snatching, [ihe odide ahụike dị mkpa] nke nje ahụ na-enweta obere, capped primers site na transcripts RNA nke mkpụrụ ndụ, nke ọ na-eji maka njikọ polymerase-catalyzed nke mRNAs nje ya dị mkpa.[17] Otu polymerase subunit na-ejikọta na pre-mRNAs na 5' caps ha, mgbe ahụ ọrụ endonuclease nke polymerase na-akpali ọwa ya "mgbe 10-13 nucleotides gasịrị". [nkwupụta ahụike dị mkpa] N'ihi ya, usoro ya dị iche na neuraminidase inhibitors dị ka oseltamivir na zanamivir.[17]

Chemistry

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Baloxavir marboxil bụ pyridone dochie anya nke sitere na ezinụlọ polycyclic, nke ụlọ ọrụ ahụ chọpụtara ya, Shionogi na Co. nke Japan (yana ndị ọzọ) kọrọ na ọ bụ kemịkal jikọtara ya n'ọtụtụ ụzọ; akụkọ ikike Shionogi apụtala ọtụtụ ugboro na akwụkwọ ndị Japan n'etiti 2016 na 2019, na-enye nghọta banyere ụzọ ndị nwere ike iji ya mee ihe.

Baloxavir marboxil (BXM) bụ ọgwụ na-arụ ọrụ nke onye na-arụsi ọrụ ike, baloxavir acid (BXA) na-ahapụ ngwa ngwa na ndụ, dịka hydrolysis nke baloxavir mar boxil na-akpali site na arylacetamide deacetylases na mkpụrụ ndụ nke ọbara, imeju, na lumen nke obere eriri afọ.[18][19][20] Nọmba ngwakọta maka baloxavir marboxil na baloxavir acid nke Shionogi na ndị ọzọ ji mee ihe n'akwụkwọ n'oge nchọpụta na mmepe (tupu e nye aha United States Adopted Name (USAN)) bụ, n'otu n'otu, S-033188 na S-033447.[21] Dị ka a kọrọ na nyocha nke akwụkwọ patent, carbonic acid ester (carbonate) nke prodrug - nke egosiri na akụkụ aka ekpe nke onyinyo ahụ dị n'elu - kwadebere n'oge nchọpụta na nyocha mmepe site na njedebe 2-hydroxy-4-pyridone precursor site na ọgwụgwọ na chloromethyl methyl carbonate.[18][22]

Akụkọ ihe mere eme

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Ka ọ na-erule Septemba 2018, na naanị akụkọ nke Phase III randomized, na-achịkwa nnwale, baloxavir belatara oge mgbaàmà influenza nke ndị na-arịa ọrịa site na ihe dị ka otu ụbọchị ma e jiri ya tụnyere otu ọgwụgwọ placebo, ma jiri ya tụnyere ihe a hụrụ maka otu ọgwụgwọ oseltamivir.[12] N'ụbọchị mbụ mgbe a malitere baloxavir n'ime otu ọgwụgwọ ya, ibu nje na-ebelata karịa ndị sonyere na oseltamivir ma ọ bụ ìgwè placebo; Otú ọ dị, mgbe ụbọchị ise gasịrị, mmetụta na ibu nje nke otu ọgwụgwọ baloxavir enweghị ike ịmata ọdịiche dị na mmetụta a hụrụ na-esote usoro zuru ezu, ụbọchị 5 nke oseltami vir na otu ọgwụgwọ ọ dị mkpa.[13]

Ọ bụ Shionogi Co., ụlọ ọrụ na-emepụta ọgwụ na Japan, na Roche AG nke dị na Switzerland mepụtara Baloxavir marboxil maka ahịa.[23] Aha ndị baloxavir marboxil na baloxavir acid pụtara na akụkọ nyocha Shionogi bụ S-033188 na S-033447, n'otu n'otu.

Ọha na omenala

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Ọnọdụ iwu

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Ministry of Health, Labour and Welfare (JMHLW) nke Japan na US Food and Drug Administration (FDA) kwadoro baloxavir marboxil dabere na ihe akaebe nke uru ya na mmetụta ndị ọzọ sitere na nnwale ahụike abụọ na ndị okenye na ụmụaka nwere influenza na-enweghị mgbagwoju anya (Nnyocha 1, 1518T0821 na Nnyocha 2, NCT02954354), nke gụnyere 1119 ndị sonyere [isi iyi dị mkpa] [nchọpụta Nnyocha ahụike abụọ gụnyere ebe na Japan, yana Nnyocha 2 na-agbakwunye ebe ahụike na United States.[24][4][12][25][4][12]

A kwadoro Baloxavir marboxil maka ire ere na Japan na Febụwarị 2018. [isi iyi N'ọnwa Ọktoba 2018, FDA kwadoro ya maka ọgwụgwọ nke influenza siri ike na-enweghị mgbagwoju anya na ndị mmadụ dị afọ iri na abụọ ma ọ bụ karịa ndị nwere mgbaàmà ruo ihe na-erughị awa 48.[7] E nyere FDA ngwa nke baloxavir marboxil nyocha mbụ na United States, ma nye Shionogi & Co., Ltd nkwado nke Xofluza n'ọnwa Ọktoba 2018.[26][7] N'ụzọ doro anya, FDA kwadoro iji baloxavir marboxil maka ndị nọ n'ihe ize ndụ dị elu nke ịrịa nsogbu metụtara influenza. N'ọnwa Ọktoba 2019, FDA kwadoro ihe ngosi emelitere maka ọgwụgwọ nke influenza siri ike, nke na-enweghị mgbagwoju anya na ndị mmadụ dị afọ iri na abụọ ma ọ bụ karịa nọ n'ihe ize ndụ nke nsogbu influenza.[8] N'ọnwa Nọvemba 2020, FDA kwadoro ihe ngosi emelitere iji tinye mgbochi mgbochi nke influenza (flu) maka ndị mmadụ dị afọ iri na abụọ ma ọ bụ karịa mgbe ha zutere onye nwere influenza.

A kwadoro Baloxavir marboxil maka iji ọgwụ mee ihe na Australia na Febụwarị 2020.

Nchebe na ịdị irè nke baloxavir marboxil, ọgwụ na-egbochi nje a na-aṅụ dị ka otu ọgwụ, gosipụtara na nnwale ahụike abụọ a na-achịkwa randomized nke mmadụ 1,832 ebe e kenyere ndị sonyere ịnata ma ọ bụ baloxavir Marboxil, placebo, ma ọ bụ ọgwụgwọ ọzọ na-egide nje n'ime awa 48 nke inwe mgbaàmà nke influenza. N'ime nnwale abụọ ahụ, ndị a gwọrọ na baloxavir marboxil nwere oge dị mkpirikpi iji belata mgbaàmà ma e jiri ya tụnyere ndị na-aṅụ placebo.[26] Na nnwale nke abụọ, ọ dịghị ihe dị iche n'oge iji belata mgbaàmà n'etiti ndị natara baloxavir marboxil na ndị natara ọgwụgwọ nke ọzọ.[26]

Nchebe na ịdị irè nke baloxavir marboxil maka mgbochi mgbochi mgbu na-akwado site na otu nnwale randomized, okpukpu abụọ, nke a na-achịkwa nke ndị mmadụ 607, afọ iri na abụọ na ndị okenye na-ahụ onye nwere influenza n'ụlọ ha, nwetara ma ọ bụ otu ọgwụ baloxavir ma ọ bụ naanị otu ọgwụ placebo. N'ime ndị a 607, 303 natara baloxavir marboxil na 304 natara placebo.[27] Isi ihe na-akpata ule ahụ bụ ọnụ ọgụgụ nke ndị butere nje influenza ma nwee ahụ ọkụ na ọ dịkarịa ala otu mgbaàmà iku ume site n'ụbọchị 1 ruo ụbọchị 10.[27] N'ime ndị natara baloxavir marboxil, 1% nke ndị ahụ ruru ụkpụrụ ndị a, ma e jiri ya tụnyere 13% nke ndị natara placebo maka nnwale ahụike.[27]

A kwadoro Baloxavir marboxil maka iji ọgwụ na European Union na Jenụwarị 2021.[5]

Ihe odide

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  1. ↑ 1.0 1.1 Xofluza Australian prescription medicine decision summary (2 March 2020). Archived from the original on 13 March 2020. Retrieved on 5 August 2023.
  2. ↑ Xofluza Product information (25 April 2012).
  3. ↑ Summary Basis of Decision (SBD) for Xofluza (23 October 2014).
  4. ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 Xofluza- baloxavir marboxil tablet, film coated. DailyMed (28 October 2019). Archived from the original on 28 October 2020. Retrieved on 9 January 2020.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 Xofluza EPAR. European Medicines Agency (EMA) (9 November 2020). Archived from the original on 30 January 2021. Retrieved on 25 January 2021.
  6. ↑ Xofluza Product information.
  7. ↑ 7.0 7.1 7.2 Drug Approval Package: Xofluza Film-Coated Tablets (Baloxavir marboxil). U.S. Food and Drug Administration (FDA) (7 December 2018). Archived from the original on 26 July 2020. Retrieved on 10 May 2020.
  8. ↑ 8.0 8.1 8.2 FDA Approval Package for 210854Orig1s001. U.S. Food and Drug Administration (FDA) (16 October 2019). Archived from the original on 9 April 2021. Retrieved on 30 September 2020.
  9. ↑ Baloxavir Marboxil for Uncomplicated Influenza: Mechanism of Action & Side Effects. Huateng Pharma. Archived from the original on 24 February 2021. Retrieved on 29 May 2020.
  10. ↑ (December 2018) "In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit". Antiviral Res. 160: 109–117. DOI:10.1016/j.antiviral.2018.10.008. PMID 30316915. 
  11. ↑ 11.0 11.1 11.2 11.3 Baloxavir Marboxil Monograph for Professionals. Drugs.com. American Society of Health-System Pharmacists (19 August 2019). Archived from the original on 7 October 2019. Retrieved on 9 January 2020.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 Drug Trial Snapshot: Xofluza. U.S. Food and Drug Administration (FDA) (23 July 2019). Archived from the original on 12 December 2019. Retrieved on 7 January 2020.
  13. ↑ 13.0 13.1 13.2 (September 2018) "Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents". N. Engl. J. Med. 379 (10): 913–923. DOI:10.1056/NEJMoa1716197. PMID 30184455. 
  14. ↑ Roche's flu med Xofluza drives drug resistance and may be a bad choice for kids, study says. FiercePharma (26 November 2019). Archived from the original on 25 November 2020. Retrieved on 8 January 2020.
  15. ↑ (January 2020) "Influenza A variants with reduced susceptibility to baloxavir isolated from Japanese patients are fit and transmit through respiratory droplets". Nature Microbiology 5 (1): 27–33. DOI:10.1038/s41564-019-0609-0. PMID 31768027. 
  16. ↑ (January 2015) "At the centre: influenza A virus ribonucleoproteins". Nature Reviews. Microbiology 13 (1): 28–41. DOI:10.1038/nrmicro3367. PMID 25417656. 
  17. ↑ 17.0 17.1 O'Hanlon (April 2019). "Baloxavir marboxil: the new influenza drug on the market". Current Opinion in Virology 35: 14–18. DOI:10.1016/j.coviro.2019.01.006. ISSN 1879-6265. PMID 30852344. Retrieved on 28 September 2020. 
  18. ↑ 18.0 18.1 Hughes (June 2019). "Review of the Patent Literature: Synthesis and Final Forms of Antiviral Drugs Tecovirimat and Baloxavir Marboxil". Organic Process Research & Development 23 (7): 1298–1307. DOI:10.1021/acs.oprd.9b00144. 
  19. ↑ (November 2019) "Molecular Dynamics Simulation reveals the mechanism by which the Influenza Cap-dependent Endonuclease acquires resistance against Baloxavir marboxil". Scientific Reports 9 (1): 17464. DOI:10.1038/s41598-019-53945-1. PMID 31767949. 
  20. ↑ (November 2018) "Evaluation of Drug-Drug Interaction Potential between Baloxavir Marboxil and Oseltamivir in Healthy Subjects". Clinical Drug Investigation 38 (11): 1053–1060. DOI:10.1007/s40261-018-0697-2. PMID 30203386. 
  21. ↑ (May 2019) "Investigational antiviral therapies for the treatment of influenza". Expert Opinion on Investigational Drugs 28 (5): 481–488. DOI:10.1080/13543784.2019.1606210. PMID 31018720. 
  22. ↑ Baloxavir Marboxil. Pharmaceutical Substances. Archived from the original on 26 July 2020. Retrieved on 8 January 2020.
  23. ↑ Branswell (27 June 2018). A flu drug — shown to reduce the duration of symptoms — could upend treatment in U.S.. Stat. Archived from the original on 20 October 2020. Retrieved on 28 June 2018.
  24. ↑ (3 November 2016) "A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza". Retrieved on 11 August 2022. 
  25. ↑ Otake. "One-dose flu drug Xofluza gets nod from health ministry", Japan Times Online, 24 February 2018. Retrieved on 8 January 2020.
  26. ↑ 26.0 26.1 26.2 Kpọpụta njehie: Invalid <ref> tag; no text was provided for refs named FDA PR 20181024
  27. ↑ 27.0 27.1 27.2 Kpọpụta njehie: Invalid <ref> tag; no text was provided for refs named FDA PR 20201123

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