Brivudine

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Brivudine
Clinical data
Trade namesZostex, Mevir, Brivir, many others
Other namesBVDU
AHFS/Drugs.comInternational Drug Names
Pregnancy
category
  • Contraindicated
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
faeces
Identifiers
  • 5-[(E)-2-bromoethenyl]-1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2,3,4-tetrahydropyrimidine-2,4-dione
JSmol)
Specific rotation+9°±1°
Density1.86 g/cm3
Melting point165 to 166 °C (329 to 331 °F) (decomposes)
  • Br[C@H]=CC=1C(=O)NC(=O)N(C=1)[C@@H]2O[C@@H]([C@@H](O)C2)CO
  • InChI=1S/C11H13BrN2O5/c12-2-1-6-4-14(11(18)13-10(6)17)9-3-7(16)8(5-15)19-9/h1-2,4,7-9,15-16H,3,5H2,(H,13,17,18)/b2-1+/t7-,8+,9+/m0/s1 checkY
  • Key:ODZBBRURCPAEIQ-PIXDULNESA-N checkY
 ☒NcheckY (what is this?)  (verify)

Brivudine (trade names Zostex, Mevir, Brivir, among others) is an

herpes zoster ("shingles"). Like other antivirals, it acts by inhibiting replication
of the target virus.

Medical uses

Brivudine is used for the treatment of herpes zoster in adult patients. It is taken orally once daily, in contrast to aciclovir, valaciclovir and other antivirals.[1] A study has found that it is more effective than aciclovir, but this has been disputed because of a possible conflict of interest on part of the study authors.[2]

Contraindications

The drug is contraindicated in patients undergoing

antimycotic drug flucytosine, which is also related to 5-FU. It has not been proven to be safe in children and pregnant or breastfeeding women.[1]

Adverse effects

The drug is generally well tolerated. The only common side effect is

anaemia, lymphocytosis, monocytosis), increased liver enzymes, and allergic reactions.[1]

Interactions

Brivudine interacts strongly and in rare cases lethally with the anticancer drug

dihydropyrimidine dehydrogenase (DPD) which is necessary for inactivating 5-FU. After a standard brivudine therapy, DPD function can be compromised for up to 18 days. This interaction is shared with the closely related drug sorivudine which also has BVU as its main metabolite.[1][3]

There are no other relevant interactions. Brivudine does not significantly influence the cytochrome P450 enzymes in the liver.[1]

Pharmacology

Spectrum of activity

The drug inhibits

inhibitory concentrations against VZV are 200- to 1000-fold lower than those of aciclovir and penciclovir, theoretically indicating a much higher potency of brivudine. Clinically relevant VZV strains are particularly sensitive.[4]

Mechanism of action

Brivudine is an analogue of the

DNA polymerases, thus inhibiting viral replication.[1][4]

Pharmacokinetics

Brivudine is well and rapidly absorbed from the gut and undergoes

first-pass metabolism in the liver, where the enzyme thymidine phosphorylase[5] quickly splits off the sugar component, leading to a bioavailability of 30%. The resulting metabolite is bromovinyluracil (BVU), which does not have antiviral activity. BVU is also the only metabolite that can be detected in the blood plasma.[1][6]

Highest blood plasma concentrations are reached after one hour. Brivudine is almost completely (>95%)

Terminal half-life is 16 hours; 65% of the substance are found in the urine and 20% in the faeces, mainly in form of an acetic acid derivative (which is not detectable in the plasma), but also other water-soluble metabolites, which are urea derivatives. Less than 1% is excreted in form of the original compound.[1]

  • Brivudine 5'-triphosphate, the active metabolite
    Brivudine 5'-triphosphate, the active metabolite
  • Bromovinyluracil (BVU), the main inactive metabolite
    Bromovinyluracil (BVU), the main inactive metabolite
  • The acetic acid derivative predominantly found in urine
    The acetic acid derivative predominantly found in urine

Chemistry

The molecule has three

stereochemically pure.[1]
The substance is a white powder.

Manufacturing

Main supplier is Berlin Chemie, now part of Italy's Menarini Group. In Central America is provided by Menarini Centro America and Wyeth.[citation needed]

History

The substance was first synthesized by scientists at the University of Birmingham in the UK in 1976. It was shown to be a potent inhibitor of HSV-1 and VZV by Erik De Clercq at the Rega Institute for Medical Research in Belgium in 1979. In the 1980s the drug became commercially available in East Germany, where it was marketed as Helpin by a pharmaceutical company called Berlin-Chemie. Only after the indication was changed to the treatment of herpes zoster in 2001 did it become more widely available in Europe.[7][8]

Brivudine is approved for use in a number of European countries including Austria, Belgium, Germany, Greece, Italy, Portugal, Spain and Switzerland.[9]

Etymology

The name brivudine derives from the chemical nomenclature bromo-vinyl-deoxyuridine or BVDU for short. It is sold under trade names such as Bridic, Brival, Brivex, Brivir, Brivirac, Brivox, Brivuzost, Zerpex, Zonavir, Zostex, and Zovudex.[9]

Research

A

herpes simplex virus epithelial keratitis. Brivudine was found to be significantly more effective than idoxuridine in increasing the number of successfully healed eyes of participants.[10]

See also

Related antiviral drugs

  • Aciclovir
  • Valacyclovir
    , a prodrug form of aciclovir
  • Famciclovir, an analogue of Penciclovir with greater oral availability
  • Foscarnet, an intravenous antiviral for aciclovir-resistant VZV
  • Penciclovir, a topical preparation

Vaccines and other treatments

  • Zostavax
    , a live virus Herpes zoster (shingles) vaccine
  • Varivax
    , a live virus Varicella Zoster (chickenpox) vaccine
  • Shingrix
    , a recombinant subunit vaccine for shingles
  • VZV immune globulin, an antibody-based treatment for immune-suppressed patients with zoster

References

  1. ^
    ISBN 978-3-85200-181-4
    .
  2. ^ "Brivudin (Zostex) besser als Aciclovir (Zovirax a.a.)?". Arznei-telegramm (in German). 5/2007.
  3. ^ "UAW – Aus Fehlern lernen - Potenziell tödlich verlaufende Wechselwirkung zwischen Brivudin (Zostex) und 5-Fluoropyrimidinen" (PDF). Deutsches Ärzteblatt (in German). 103 (27). 7 July 2006.
  4. ^
    ISBN 3-7692-3483-9
    .
  5. PMID 6651877
    .
  6. ISBN 3-8047-1763-2
    .
  7. PMID 15548377
    .
  8. ^ Tringali C, ed. (2012). Bioactive Compounds from Natural Sources (2nd ed.). CRC Press. p. 170.
  9. ^ a b "Brivudine". drugs.com.
  10. PMID 25879115
    .
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