Viramidine

Viramidine

File:Viramidine.png
Clinical data
Synonyms	1-(β-D-Ribofuranosyl)- 1,2,4-triazole-3-carboximide
Pregnancy category	X
Routes of administration	Oral capsule
ATC code	J05AB04 (WHO)
Legal status
Legal status	In Phase III drug trials
Pharmacokinetic data
Bioavailability	9%
Metabolism	Metabolized to 5'phosphates, de-riboside, and deriboside carboxylic acid
Elimination half-life	12 days - Multiple Dose; 120-170 hours - Single Dose
Excretion	10% fecal, remainder in urine (30% unchanged, remainder metabolites)
Identifiers
IUPAC name 1-[(2R,3R,4S,5S)- 3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl]- 1,2,4-triazole-3-carboximidamide
CAS Number	119567-79-2
PubChem CID	451448
DrugBank	none
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C8H13N5O4
Molar mass	243.220 g/mol (279.681 g/mol for HCl salt)

Viramidine (ICN 3142, also known as taribavirin) is an anti-viral 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. Viramidine 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.

Viramidine 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.

Viramidine is being developed by Valeant Pharmaceuticals International, the parent company of Ribapharm, the company which first reported synthesis and testing of the drug in 1973. Valeant is testing the drug as a treatment for chronic hepatitis C.

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.

References

1. Barnard, D (2002). "Viramidine (Ribapharm)". Current Opinion in Investigational Drugs. 3 (11): 1585–9.
2. Gish, Robert G. (2006). "Treating HCV with ribavirin analogues and ribavirin-like molecules". Journal of Antimicrobial Chemotherapy. 57 (1): 8–13. doi:10.1093/jac/dki405. PMID 16293677.
3. Lin, Chin-Chung (2003). "Pharmacokinetics and Metabolism of 14C Viramidine in Rats and Cynomolgus Monkeys". Antimicrob Agents Chemother. 47 (8): 458–2463.
4. Sidwell, RW (2005). "In vitro and in vivo influenza virus-inhibitory effects of viramidine". Antiviral Research. 68 (1): 8–13. PMID 16087250.
5. Witkowski, J. T. (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: 935–7.