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Antimicrobial Agents and Chemotherapy, October 2004, p. 4006-4008, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.4006-4008.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Dual-Action Mechanism of Viramidine Functioning as a Prodrug and as a Catabolic Inhibitor for Ribavirin

Jim Zhen Wu,* Gary Larson, and Zhi Hong

Drug Discovery, R&D, Valeant Pharmaceuticals International, Costa Mesa, California

Received 24 March 2004/ Returned for modification 25 May 2004/ Accepted 8 June 2004

An investigational nucleoside analogue drug, viramidine, has recently emerged as a potentially safer alternative to ribavirin for the treatment of hepatitis C viral infection. We have reported that viramidine mainly functions as a prodrug of ribavirin that is enriched in the liver. This in vitro study further explores viramidine's activity against nucleoside phosphorylase, a host enzyme that is responsible for phosphorolysis of ribavirin in vivo. Our experiments show that viramidine inhibits ribavirin phosphorolysis with a Ki of 2.5 µM. This result suggests that viramidine may act through a dual-action mechanism by serving as a prodrug of ribavirin and concomitantly as an inhibitor for nucleoside phosphorylase catabolism of ribavirin.

* Corresponding author. Mailing address: Drug Discovery, R&D, Valeant Pharmaceuticals International, 3300 Hyland Ave., Costa Mesa, CA 92626. Phone: (714) 545-0100, ext. 3024. Fax: (714) 668-3142. E-mail: jwu{at}valeant.com.

Antimicrobial Agents and Chemotherapy, October 2004, p. 4006-4008, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.4006-4008.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wu, J. Z., Larson, G., Walker, H., Shim, J. H., Hong, Z. (2005). Phosphorylation of Ribavirin and Viramidine by Adenosine Kinase and Cytosolic 5'-Nucleotidase II: Implications for Ribavirin Metabolism in Erythrocytes. Antimicrob. Agents Chemother. 49: 2164-2171 [Abstract] [Full Text]  


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