Discovery and development of BVDU (brivudin) as a therapeutic for the treatment of herpes zoster.

Abstract

This Commentary is dedicated to the memory of Dr. Jacques Gielen, the late Editor of Biochemical Pharmacology, whom I have known as both an author and reviewer for the Journal for about 25 years. This is, quite incidentally, about the time it took for bringing brivudin (BVDU) [(E)-5-(2-bromovinyl)-2'-deoxyuridine] from its original description as an antiviral agent to the market place (in a number of European countries, including Germany and Italy) for the treatment of herpes zoster in immunocompetent persons. BVDU is exquisitely active and selective against varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1). BVDU owes this high selectivity and activity profile to a specific phosphorylation by the virus-encoded thymidine kinase, followed by a potent interaction with the viral DNA polymerase. The (E)-5-(2-bromovinyl)-substituent can be considered as the hallmark for the activity of BVDU against VZV and HSV-1. Extensive clinical studies have indicated that BVDU as a single (oral) daily dose of 125 mg (for no more than 7 days) is effective in the treatment of herpes zoster, as regards both short-term (suppression of new lesion formation) and long-term effects (prevention of post-herpetic neuralgia). In this sense, BVDU is as efficient and/or convenient, if not more so, than the other drugs (acyclovir, valaciclovir, famciclovir) that have been licensed for the treatment of herpes zoster. There is one caveat; however, BVDU should not be given to patients under 5-fluorouracil therapy, as the degradation product of BVDU, namely (E)-5-(2-bromovinyl)uracil (BVU), may potentiate the toxicity of 5-fluorouracil, due to inhibition of dihydropyrimidine dehydrogenase, the enzyme involved in the catabolism of 5-fluorouracil.

• Authors: E De Clercq
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 68 Issue 12 Pg. 2301-15 (Dec 15 2004) ISSN: 0006-2952 [Print] England
• PMID: 15548377 (Publication Type: Journal Article, Review)

Chemical References

• Antimetabolites
• Antiviral Agents
• brivudine
• Bromodeoxyuridine
• Fluorouracil

Topics

• Antimetabolites (pharmacology)
• Antiviral Agents (therapeutic use)
• Bromodeoxyuridine (analogs & derivatives, therapeutic use)
• Drug Interactions
• Europe
• Fluorouracil (pharmacology)
• Herpes Zoster (drug therapy)
• Herpesvirus 3, Human (drug effects)
• Humans
• Virus Replication (drug effects)