Artesunate/pyronaridine

Artesunate/pyronaridine, sold under the brand name Pyramax, is a fixed-dose combination medication for the treatment of malaria.[3][1] It can be used for malaria of both the P. falciparum and P. vivax types.[1] It combines artesunate and pyronaridine.[3] It is taken by mouth.[2]

Artesunate/pyronaridine
Combination of
ArtesunateAntimalarial
PyronaridineAntimalarial
Clinical data
Trade namesPyramax[1]
Other namesArtesunate/pyronaridine tetraphosphate[1]
Routes of
administration		By mouth[2]
ATC code
Identifiers
CAS Number

The combination is generally well tolerated.[1] Side effects may include headache, vomiting, or cough.[1] Use in those with severe liver disease or kidney disease is not recommended.[2] Use is not generally recommended in early pregnancy.[2] However, there are no other options and if treatment may save the mother's life it may be used.[2] The two components work by different mechanisms.[2]

It is on the World Health Organization's List of Essential Medicines.[3]

Medical uses

Artesunate/pyronaridine is used for malaria of both the P. falciparum and P. vivax types.[1] It is not recommended for severe disease.[2]

A 2019 review found that the combination compared well to artemether/lumefantrine.[4] Benefits also appear similar to mefloquine together with artesunate.[4] It is not recommended for the prevention of malaria.[2]

Research for drug repurposing

It has also been studied as a potential anticancer drug,[5] treatment for Ebola[6]

It was announced on 3 April 2020 that artesunate/pyronaridine, the main components of a new ACT antimalarial drug sold under the brand name Pyramax, showed an inhibitory effect on SARS-CoV-2 Pyramax showed a virus titer inhibition rate of 99% or more after 24 hours in vitro tests using Hela cells. , while cytotoxicity was also reduced.[7]

A preprint published in July 2020 reported that pyronaridine and artesunate exhibit antiviral activity against SARS-CoV-2 and influenza viruses using human lung epithelial (Calu-3) cells and Vero cells.[8] This in vitro experiment was very important in that the human lung cell Calu-3 was used, the cells were first infected with SARS-COV-2 and then treated with drugs 1 hour later.

Also, this in vitro experiment is encouraging in that the combination of pyronaridine and artesunate showed 100% inhibition in Vero cells. When each component was tested in Vero cells, the effect was less than that of HCQ, but when the two components were combined, it showed 100% inhibition and the effect lasted 48 hours. This shows that the two ingredients have a synergistic effect.

When tested in calu-3 cells with a single component of PYR and ART, the inhibition rate was 80-90%, especially the SI value of ART was very high, reaching 220.

The combination of pyronaridine and artesunate is being studied as a possible treatment for moderate to severe SARS-COV-2. [9] The preprint[8] published in July 2020 is cited as a reference paper for this paper.[9]

It is currently in phase II clinical trial in South Korea, South Africaand Philippine. phase III clinical trial in Burkina Faso, Kenya. The clinical trials in Burkina Faso, Kenya are led by CDC in the USA and The Liverpool School of Tropical Medicine in the UK.

References
  1. "Application for inclusion in the WHO Model List of essential medicines" (PDF). WHO. Nov 2010. Retrieved 29 June 2017.
  2. "Pyramax 180 mg/60 mg Film-coated tablet" (PDF). EMA. Retrieved 13 December 2017.
  3. World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  4. Pryce J, Hine P (January 2019). "Pyronaridine-artesunate for treating uncomplicated Plasmodium falciparum malaria". The Cochrane Database of Systematic Reviews. 1: CD006404. doi:10.1002/14651858.CD006404.pub3. PMC 6353203. PMID 30620055.
  5. Villanueva PJ, Martinez A, Baca ST, DeJesus RE, Larragoity M, Contreras L, et al. (2018-11-05). "Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis". PLOS ONE. 13 (11): e0206467. Bibcode:2018PLoSO..1306467V. doi:10.1371/journal.pone.0206467. PMC 6218039. PMID 30395606.
  6. Lane TR, Massey C, Comer JE, Anantpadma M, Freundlich JS, Davey RA, et al. (November 2019). "Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection". PLOS Neglected Tropical Diseases. 13 (11): e0007890. doi:10.1371/journal.pntd.0007890. PMC 6894882. PMID 31751347.
  7. "'피라맥스' 약물 재창출?…코로나19 치료제 타진". 의협신문 (in Korean). 2020-04-03. Retrieved 2021-02-27.
  8. Bae, Joon-Yong; Lee, Gee Eun; Park, Heedo; Cho, Juyoung; Kim, Yung-Eui; Lee, Joo-Yeon; Ju, Chung; Kim, Won-Ki; Kim, Jin Il; Park, Man-Seong (2020-07-28). "Pyronaridine and artesunate are potential antiviral drugs against COVID-19 and influenza". bioRxiv: 2020.07.28.225102. doi:10.1101/2020.07.28.225102. S2CID 220885187.
  9. Krishna, Sanjeev; Augustin, Yolanda; Wang, Jigang; Xu, Chengchao; Staines, Henry M.; Platteeuw, Hans; Kamarulzaman, Adeeba; Sall, Amadou; Kremsner, Peter (2021-01-01). "Repurposing Antimalarials to Tackle the COVID-19 Pandemic". Trends in Parasitology. 37 (1): 8–11. doi:10.1016/j.pt.2020.10.003. ISSN 1471-4922. PMC 7572038. PMID 33153922.
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