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.
Pharmacology
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.
Microbiology
Aciclovir, the active metabolite of valaciclovir, is active against most species in the
herpesvirus family. In descending order of activity:
[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]
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[ Valaciclovir ]
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