Valaciclovir
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Valaciclovir
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| Systematic (IUPAC) name | |
| 2-[(2-amino-6-oxo-3,9-dihydropurin-9-yl)methoxy] ethyl-2-amino-3-methyl-butanoate |
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| Identifiers | |
| CAS number | 124832-27-5 |
| ATC code | J05AB11 |
| PubChem | 60773 |
| DrugBank | APRD00697 |
| Chemical data | |
| Formula | C13H20N6O4 |
| Mol. weight | 324.336 g/mol |
| Pharmacokinetic data | |
| Bioavailability | 55% |
| Protein binding | 13–18% |
| Metabolism | Hepatic (to aciclovir) |
| Half life | <30 minutes (valaciclovir); 2.5-3.6 hours (aciclovir) |
| Excretion | Renal 40–50% (aciclovir), faecal 47% (aciclovir) |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status |
S4 (Au), POM (UK), ℞-only (U.S.) |
| Routes | Oral |
Valaciclovir (INN) or valacyclovir (USAN) is an antiviral drug used in the management of herpes simplex and herpes zoster (shingles). It is a prodrug, being converted in vivo to aciclovir. It is marketed by GlaxoSmithKline under the trade name Valtrex.
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[edit] Pharmacology
[edit] Mechanism of action
Valaciclovir is a prodrug that is converted by esterases to the active drug aciclovir via hepatic first-pass metabolism. Aciclovir is selectively converted into a monophosphate form by viral thymidine kinase, which is far more effective (3000 times) in phosphorylation than cellular thymidine kinase. Subsequently, the monophosphate form is further phosphorylated into the active triphosphate form, aciclo-GTP, by cellular kinases. Aciclo-GTP is a very potent inhibitor of viral DNA polymerase; it has approximately 100 times higher affinity to viral than cellular polymerase. Its monophosphate form also incorporates into the viral DNA, resulting in chain termination. It has also been shown that the viral enzymes cannot remove aciclo-GMP from the chain, which results in inhibition of further activity of DNA polymerase. Aciclo-GTP is fairly rapidly metabolised within the cell, possibly by cellular phosphatases.
[edit] Microbiology
Aciclovir, the active metabolite of valaciclovir, is active against most species in the herpesvirus family. In descending order of activity:[1]
- Herpes simplex virus type I (HSV-1)
- Herpes simplex virus type II (HSV-2)
- Varicella zoster virus (VZV)
- Epstein-Barr virus (EBV)
- Cytomegalovirus (CMV)
Activity is predominantly active against HSV, and to a lesser extent VZV. It is only of limited efficacy against EBV and CMV. It is inactive against latent viruses in nerve ganglia.
To date, resistance to valaciclovir has not been clinically significant. Mechanisms of resistance in HSV include deficient viral thymidine kinase; and mutations to viral thymidine kinase and/or DNA polymerase, altering substrate sensitivity.[2]
[edit] Clinical use
[edit] Indications
Valaciclovir is indicated for the treatment of HSV and VZV infections, including:[3]
- Genital herpes simplex (treatment and prophylaxis)
- Reduction of HSV transmission from people with recurrent infection to uninfected individuals
- Herpes zoster (shingles)
- Prevention of CMV disease following organ transplantation
[edit] Adverse effects
Common adverse drug reactions (≥1% of patients) associated with valaciclovir therapy are the same as for aciclovir, its active metabolite, and include: nausea, vomiting, diarrhoea and/or headache. Infrequent adverse effects (0.1–1% of patients) include: agitation, vertigo, confusion, dizziness, oedema, arthralgia, sore throat, constipation, abdominal pain, rash, weakness and/or renal impairment. Rare adverse effects (<0.1% of patients) include: coma, seizures, neutropenia, leukopenia, tremor, ataxia, encephalopathy, psychotic
[edit] References
- ^ O'Brien JJ, Campoli-Richards DM. Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1989;37(3):233-309. PMID 2653790
- ^ Sweetman S, editor. Martindale: The complete drug reference. 34th ed. London: Pharmaceutical Press; 2004. ISBN 0-85369-550-4
- ^ Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
[edit] External links
| Antivirals (primarily J05A, also S01AD and D06BB) edit | ||||||||||||||||||||||
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