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{{short description|Antiviral drug}}
{{distinguish|text=tribavirin, which is [[ribavirin]]}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| Verifiedfields = changed
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| verifiedrevid = 470477612
| verifiedrevid = 470477612
| IUPAC_name = 1-[(2''R'',3''R'',4''S'',5''R'')- 3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl]- 1,2,4-triazole-3-carboximidamide
| IUPAC_name = 1-[(2''R'',3''R'',4''S'',5''R'')- 3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl]- 1,2,4-triazole-3-carboximidamide
| image = Viramidine.svg
| image = Taribavirin.svg
| width = 134
| width = 175
| image2 = Taribavirin 3D spacefill.png
| width2 = 215
| alt2 = Ball-and-stick model of the taribavirin molecule


<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename =
| pregnancy_category = X
| pregnancy_category = X
| legal_status = In Phase III drug trials
| legal_status = In Phase III drug trials
| routes_of_administration = Oral capsule
| routes_of_administration = Oral [[Capsule (pharmacy)|capsules]])


<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
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| UNII = R3B1994K2E
| UNII = R3B1994K2E
| NIAID_ChemDB = 000198
| NIAID_ChemDB = 000198
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D06651


<!--Chemical data-->
<!--Chemical data-->
| C=8 | H=13 | N=5 | O=4
| C=8 | H=13 | N=5 | O=4
⚫
| SMILES = n1c(nn(c1)[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)CO)C(=[N@H])N
| molecular_weight = 243.220 g/mol (279.681 g/mol for [[hydrochloride|HCl]] salt)
⚫
| smiles = n1c(nn(c1)[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)CO)C(=[N@H])N
| InChI = 1/C8H13N5O4/c9-6(10)7-11-2-13(12-7)8-5(16)4(15)3(1-14)17-8/h2-5,8,14-16H,1H2,(H3,9,10)/t3-,4-,5-,8-/m1/s1
| InChIKey = NHKZSTHOYNWEEZ-AFCXAGJDBX
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C8H13N5O4/c9-6(10)7-11-2-13(12-7)8-5(16)4(15)3(1-14)17-8/h2-5,8,14-16H,1H2,(H3,9,10)/t3-,4-,5-,8-/m1/s1
| StdInChI = 1S/C8H13N5O4/c9-6(10)7-11-2-13(12-7)8-5(16)4(15)3(1-14)17-8/h2-5,8,14-16H,1H2,(H3,9,10)/t3-,4-,5-,8-/m1/s1
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| synonyms = 1-(β-<small>D</small>-Ribofuranosyl)-<br>1,2,4-triazole-3-carboximide
| synonyms = 1-(β-<small>D</small>-Ribofuranosyl)-<br>1,2,4-triazole-3-carboximide
}}
}}

'''Taribavirin''' ([[International Nonproprietary Name|rINN]]; also known as '''viramidine''', codenamed '''ICN 3142''') is an [[antiviral drug]] in [[clinical trial#Phase III|Phase III]] human trials, but not yet approved for pharmaceutical use. It is a [[prodrug]] of [[ribavirin]], active against a number of [[DNA]] and [[RNA]] [[virus]]es. Taribavirin has better liver-targeting than ribavirin, and has a shorter life in the body due to less penetration and storage in [[red blood cells]]. It is expected eventually to be the drug of choice for viral hepatitis syndromes in which ribavirin is active. These include [[hepatitis C]] and perhaps also [[hepatitis B]] and [[yellow fever]].
'''Taribavirin''' ([[International Nonproprietary Name|rINN]]; also known as '''viramidine''', codenamed '''ICN 3142''') is an [[antiviral drug]] in [[clinical trial#Phase III|Phase III]] human trials, but not yet approved for pharmaceutical use. It is a [[prodrug]] of [[ribavirin]], active against a number of [[DNA]] and [[RNA]] [[virus]]es. Taribavirin has better liver-targeting than ribavirin, and has a shorter life in the body due to less penetration and storage in [[red blood cells]]. It is expected eventually to be the drug of choice for viral hepatitis syndromes in which ribavirin is active. These include [[hepatitis C]] and perhaps also [[hepatitis B]] and [[yellow fever]].


==Uses==
==Uses==
Taribavirin is as active against influenza as ribavirin in animal models, with slightly less toxicity, so it may also eventually replace ribavirin as an anti-influenza agent.
Taribavirin is as active against [[influenza]] as ribavirin in animal models, with slightly less toxicity, so it may also eventually replace ribavirin as an anti-influenza agent.{{cn|date=November 2022}}


==History==
==History==
Taribavirin was first reported in 1973 by J.T.Witkowski et al.,<ref>{{cite journal | pmid = 4355593 | doi=10.1021/jm00266a014 | volume=16 | issue=8 | title=Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides |date=August 1973 | journal=J. Med. Chem. | pages=935–7}}</ref> then working at ICN Pharmaceuticals, in an attempt to find a more active derivative of ribavirin. Taribavirin is presently being developed by [[Valeant Pharmaceuticals International]]. Valeant is testing the drug as a treatment for chronic hepatitis C.
Taribavirin was first reported in 1973 by J. T. Witkowski et al.,<ref>{{cite journal | vauthors = Witkowski JT, Robins RK, Khare GP, Sidwell RW | title = Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides | journal = Journal of Medicinal Chemistry | volume = 16 | issue = 8 | pages = 935–7 | date = August 1973 | pmid = 4355593 | doi = 10.1021/jm00266a014 }}</ref> then working at ICN Pharmaceuticals, in an attempt to find a more active derivative of ribavirin. Taribavirin is being developed by [[Valeant Pharmaceuticals International]]. Valeant is testing the drug as a treatment for chronic hepatitis C.{{cn|date=November 2022}}


==Pharmacology==
==Pharmacology==
Note on formulas: The carboxamidine group of this molecule is somewhat basic, and therefore this drug is also known and administered as the hydrochloride salt (with a corresponding .HCl chemical formula and different ChemID / PubChem number). At physiologic pH, the positive charge on the molecule from partial protonation of the carboximide group contributes to the relative slowness with which the drug crosses cell membranes (such as in red blood cells) until it has been metabolized into [[ribavirin]]. In the liver, however, the transformation from carboxamidine to carboxamide happens on first-pass metabolism and contributes to the higher levels of ribavirin found in liver cells and bile when viramidine is administered.
Note on formulas: The carboxamidine group of this molecule is somewhat basic, and therefore this drug is also known and administered as the hydrochloride salt (with a corresponding HCl chemical formula and different ChemID / PubChem number). At physiologic pH, the positive charge on the molecule from partial protonation of the carboximide group contributes to the relative slowness with which the drug crosses cell membranes (such as in red blood cells) until it has been metabolized into [[ribavirin]]. In the liver, however, the transformation from carboxamidine to carboxamide happens on first-pass metabolism and contributes to the higher levels of ribavirin found in liver cells and bile when viramidine is administered.{{cn|date=January 2023}}


==Notes==
==Notes==
{{Reflist}}
{{Reflist}}


==References==
== References ==
{{More footnotes|date=April 2009}}
{{More footnotes|date=April 2009}}
<!-- Please add new references in alphabetical order by last name of first author-->
<!-- Please add new references in alphabetical order by last name of first author-->
<div style="font-size:90%">
<div style="font-size:90%">
# {{cite journal | vauthors = Barnard D | title = Viramidine (Ribapharm) | journal = Current Opinion in Investigational Drugs | volume = 3 | issue = 11 | pages = 1585–9 | date = November 2002 | pmid = 12476957 }}
# {{cite journal
# {{cite journal | vauthors = Gish RG | title = Treating HCV with ribavirin analogues and ribavirin-like molecules | journal = The Journal of Antimicrobial Chemotherapy | volume = 57 | issue = 1 | pages = 8–13 | date = January 2006 | pmid = 16293677 | doi = 10.1093/jac/dki405 | doi-access = }}
| last = Barnard
# {{cite journal | vauthors = Lin CC, Luu K, Lourenco D, Yeh LT | title = Pharmacokinetics and metabolism of [14C]viramidine in rats and cynomolgus monkeys | journal = Antimicrobial Agents and Chemotherapy | volume = 47 | issue = 8 | pages = 2458–63 | date = August 2003 | pmid = 12878505 | pmc = 166067 | doi = 10.1128/aac.47.8.2458-2463.2003 }}
| first = D
# {{cite journal | vauthors = Sidwell RW, Bailey KW, Wong MH, Barnard DL, Smee DF | title = In vitro and in vivo influenza virus-inhibitory effects of viramidine | journal = Antiviral Research | volume = 68 | issue = 1 | pages = 10–7 | date = October 2005 | pmid = 16087250 | doi = 10.1016/j.antiviral.2005.06.003 }}
| authorlink =
# {{cite journal | vauthors = Witkowski JT, Robins RK, Khare GP, Sidwell RW | title = Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides | journal = Journal of Medicinal Chemistry | volume = 16 | issue = 8 | pages = 935–7 | date = August 1973 | pmid = 4355593 | doi = 10.1021/jm00266a014 }}
| title = Viramidine (Ribapharm)
| journal = Current Opinion in Investigational Drugs
| volume = 3
| issue = 11
| pages = 1585–9
| publisher =
| year = 2002
| doi =
| id =
| accessdate =
| pmid = 12476957 }}
# {{cite journal
| last = Gish
| first = Robert G.
|date=January 2006
| title = Treating HCV with ribavirin analogues and ribavirin-like molecules
| journal = [[Journal of Antimicrobial Chemotherapy]]
| volume = 57
| issue = 1
| pages = 8–13
| pmid = 16293677
| doi = 10.1093/jac/dki405
}}
# {{cite journal
| last = Lin
| first = Chin-Chung
| authorlink =
| coauthors = Kenneth Luu, David Lourenco, and Li-Tain Yeh
| title = Pharmacokinetics and Metabolism of 14CViramidine in Rats and Cynomolgus Monkeys
| journal = Antimicrob Agents Chemother
| volume = 47
| issue = 8
| pages = 458–2463
| publisher =
| year = 2003
| doi =
| id =
| accessdate =
| pmc=166067
| pmid=12878505}}
# {{cite journal
| last = Sidwell
| first = RW
|author2=Bailey KW |author3=Wong MH |author4=Barnard DL |author5=Smee DF
|date=October 2005
| title = In vitro and in vivo influenza virus-inhibitory effects of viramidine
| journal = Antiviral Research
| volume = 68
| issue = 1
| pages = 8–13
| pmid = 16087250
| doi = 10.1016/j.antiviral.2005.06.003
}}
# {{cite journal
| last = Witkowski
| first = J. T.
| authorlink =
| coauthors = Robins, R. K., Khare, G. P. et al.
| title = Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides
| journal = Journal of Medicinal Chemistry
| volume = 16
| issue = 8
| pages = 935–7
| publisher =
| year = 1973
| doi = 10.1021/jm00266a014
| id =
| accessdate =
| pmid = 4355593 }}
</div>
</div>


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{{RNA antivirals}}
{{RNA antivirals}}


[[Category:Anti-RNA virus drugs]]
[[Category:Anti–RNA virus drugs]]
[[Category:Prodrugs]]
[[Category:Prodrugs]]
[[Category:Triazoles]]
[[Category:Triazoles]]
[[Category:Amidines]]
[[Category:Amidines]]
[[Category:Experimental antiviral drugs]]

Latest revision as of 06:47, 31 December 2023

Not to be confused with tribavirin, which is ribavirin.
Taribavirin
Ball-and-stick model of the taribavirin molecule
Clinical data
Other names1-(β-D-Ribofuranosyl)-
1,2,4-triazole-3-carboximide
Pregnancy
category
  • X
Routes of
administration		Oral capsules)
ATC code
Legal status
Legal status
  • In Phase III drug trials
Pharmacokinetic data
Bioavailability9%
MetabolismMetabolized to 5'phosphates, de-riboside, and deriboside carboxylic acid
Elimination half-life12 days - Multiple Dose; 120-170 hours - Single Dose
Excretion10% fecal, remainder in urine (30% unchanged, remainder metabolites)
Identifiers
  • 1-[(2R,3R,4S,5R)- 3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl]- 1,2,4-triazole-3-carboximidamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
NIAID ChemDB
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC8H13N5O4
Molar mass243.223 g·mol−1
3D model (JSmol)
  • n1c(nn(c1)[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)CO)C(=[N@H])N
  • InChI=1S/C8H13N5O4/c9-6(10)7-11-2-13(12-7)8-5(16)4(15)3(1-14)17-8/h2-5,8,14-16H,1H2,(H3,9,10)/t3-,4-,5-,8-/m1/s1 checkY
  • Key:NHKZSTHOYNWEEZ-AFCXAGJDSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Taribavirin (rINN; also known as viramidine, codenamed ICN 3142) is an antiviral drug in Phase III human trials, but not yet approved for pharmaceutical use. It is a prodrug of ribavirin, active against a number of DNA and RNA viruses. Taribavirin has better liver-targeting than ribavirin, and has a shorter life in the body due to less penetration and storage in red blood cells. It is expected eventually to be the drug of choice for viral hepatitis syndromes in which ribavirin is active. These include hepatitis C and perhaps also hepatitis B and yellow fever.

Uses

[edit]

Taribavirin is as active against influenza as ribavirin in animal models, with slightly less toxicity, so it may also eventually replace ribavirin as an anti-influenza agent.[citation needed]

History

[edit]

Taribavirin was first reported in 1973 by J. T. Witkowski et al.,[1] then working at ICN Pharmaceuticals, in an attempt to find a more active derivative of ribavirin. Taribavirin is being developed by Valeant Pharmaceuticals International. Valeant is testing the drug as a treatment for chronic hepatitis C.[citation needed]

Pharmacology

[edit]

Note on formulas: The carboxamidine group of this molecule is somewhat basic, and therefore this drug is also known and administered as the hydrochloride salt (with a corresponding HCl chemical formula and different ChemID / PubChem number). At physiologic pH, the positive charge on the molecule from partial protonation of the carboximide group contributes to the relative slowness with which the drug crosses cell membranes (such as in red blood cells) until it has been metabolized into ribavirin. In the liver, however, the transformation from carboxamidine to carboxamide happens on first-pass metabolism and contributes to the higher levels of ribavirin found in liver cells and bile when viramidine is administered.[citation needed]

Notes

[edit]
  1. ^ Witkowski JT, Robins RK, Khare GP, Sidwell RW (August 1973). "Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides". Journal of Medicinal Chemistry. 16 (8): 935–7. doi:10.1021/jm00266a014. PMID 4355593.

References

[edit]
  1. Barnard D (November 2002). "Viramidine (Ribapharm)". Current Opinion in Investigational Drugs. 3 (11): 1585–9. PMID 12476957.
  2. Gish RG (January 2006). "Treating HCV with ribavirin analogues and ribavirin-like molecules". The Journal of Antimicrobial Chemotherapy. 57 (1): 8–13. doi:10.1093/jac/dki405. PMID 16293677.
  3. Lin CC, Luu K, Lourenco D, Yeh LT (August 2003). "Pharmacokinetics and metabolism of [14C]viramidine in rats and cynomolgus monkeys". Antimicrobial Agents and Chemotherapy. 47 (8): 2458–63. doi:10.1128/aac.47.8.2458-2463.2003. PMC 166067. PMID 12878505.
  4. Sidwell RW, Bailey KW, Wong MH, Barnard DL, Smee DF (October 2005). "In vitro and in vivo influenza virus-inhibitory effects of viramidine". Antiviral Research. 68 (1): 10–7. doi:10.1016/j.antiviral.2005.06.003. PMID 16087250.
  5. Witkowski JT, Robins RK, Khare GP, Sidwell RW (August 1973). "Synthesis and antiviral activity of 1,2,4-triazole-3-thiocarboxamide and 1,2,4-triazole-3-carboxamidine ribonucleosides". Journal of Medicinal Chemistry. 16 (8): 935–7. doi:10.1021/jm00266a014. PMID 4355593.
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