General
Preferred name
valaciclovir
Synonyms
VALACYCLOVIR HYDROCHLORIDE ()
Valaciclovir hydrochloride ()
Valaciclovir HCl ()
Valtrex ()
2-[(2-amino-6-oxo-6,9-dihydro-1H-purin-9-yl)methoxy]ethyl (2S)-2-amino-3-methylbutanoate hydrochloride ()
Valacyclovir (hydrochloride) ()
valacyclovir ()
BW-256 ()
BW-256U87 ()
256-U-87 HYDROCHLORIDE ()
NSC-759101 ()
Valaciclovir (as hydrochloride) ()
Valacyclovir hcl ()
256U87 HYDROCHLORIDE ()
Zelitrex ()
Valacv ()
L-Valacyclovir (hydrochloride) ()
L-Valacyclovir-d8 (hydrochloride) ()
P&D ID
PD009909
CAS
124832-26-4
124832-27-5
1279033-32-7
Tags
available
drug
prodrug
Approved by
FDA
First approval
1995
Drug indication
Herpes simplex virus infection
Virus infection
Antiviral
Drug Status
approved
investigational
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE
The plasma elimination half-life of acyclovir typically averaged 2.5 to 3.3 hours in several studies of valacyclovir in volunteers with normal renal function [FDA label].
INDICATION
Valacyclovir is a nucleoside analog DNA polymerase inhibitor indicated for [FDA label]: **Adults** ⢠Cold Sores (Herpes Labialis) ⢠Genital Herpes ⢠Treatment of genital herpes lesions in immunocompetent patients (initial or recurrent episode) ⢠Suppression of genital herpes lesions in immunocompetent or HIV-infected patients ⢠Reduction of viral transmission ⢠Herpes Zoster **Pediatric Patients** ⢠Cold Sores (Herpes Labialis) ⢠Chickenpox **Limitations of use** [FDA label] The efficacy and safety of valacyclovir have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.
ROE
After oral administration of a single 1 gram dose of radiolabeled valacyclovir to 4 healthy subjects, 46% and 47% of administered radioactivity was measured in urine and feces, respectively, over 96 hours. Acyclovir accounted for 89% of the radioactivity excreted in the urine [FDA label].
METABOLISM
Valacyclovir is converted to acyclovir and L-valine via first-pass intestinal and/or hepatic metabolism. Acyclovir is also transformed, to a small extent, to inactive metabolites by _aldehyde oxidase_ in addition to _alcohol dehydrogenase_ and _aldehyde dehydrogenase_. Neither valacyclovir nor acyclovir is metabolized by cytochrome P450 enzymes [FDA label].
ABSORPTION
After oral administration, valacyclovir hydrochloride is rapidly absorbed from the gastrointestinal (GI) tract and converted to acyclovir and L-valine. The absolute bioavailability of acyclovir after administration of valacyclovir was measured at 54.5% ± 9.1% after the administration of a 1 gram oral dose of valacyclovir and a 350 mg intravenous (IV) acyclovir dose to 12 healthy subjects. Acyclovir (a metabolite of valacyclovir) bioavailability from the administration of this drug is not affected by the administration with food [FDA label].
INDICATION
Valacyclovir is a nucleoside analog DNA polymerase inhibitor indicated for [FDA label]: ; ; **Adults**; ; ⢠Cold Sores (Herpes Labialis); ; ⢠Genital Herpes; ; ⢠Treatment of genital herpes lesions in immunocompetent patients (initial or recurrent episode); ; ⢠Suppression of genital herpes lesions in immunocompetent or HIV-infected patients; ; ⢠Reduction of viral transmission; ; ⢠Herpes Zoster; ; **Pediatric Patients** ; ; ⢠Cold Sores (Herpes Labialis); ; ⢠Chickenpox ; ; ; ; **Limitations of use** [FDA label]; ; The efficacy and safety of valacyclovir have not been established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.;
DESCRIPTION
Valacyclovir s an esterified prodrug, which is converted to in vivo. Esterification increases the oral bioavailability of the prodrug compared to the parent molecule.
(GtoPdb)
MOA
Valacyclovir is the L-valine ester of aciclovir. It is classified as a nucleoside analog DNA polymerase enzyme inhibitor. Aciclovir is a purine (guanine) nucleoside analog is a metabolite that heavily contributes to the pharmacological actions of valacyclovir. In fact, most of valacyclovir's activity is attributed to acyclovir [A175885]. Valacyclovir is rapidly and almost completely converted in man to aciclovir and valine, likely by the enzyme _valacyclovir hydrolase_. Aciclovir is a selective inhibitor of the herpes viruses, possessing in vitro activity against herpes simplex viruses (HSV) type 1 and type 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr Virus (EBV), as well as human herpesvirus 6 (HHV-6). Aciclovir has been shown to inhibit herpes virus DNA synthesis after it has been phosphorylated to the active triphosphate form [F3949]. The first stage of drug phosphorylation for acyclovir requires activation by a virus-specific enzyme. In the case of HSV, VZV and EBV this enzyme is the viral _thymidine kinase_ (TK), which is only found in virus-infected cells. The process of phosphorylation is completed (conversion from mono- to triphosphate) by cellular kinases. Acyclovir triphosphate competitively inhibits the virus DNA polymerase and incorporation of this agent results in DNA chain termination, stopping virus DNA synthesis and blocking virus replication [F3949]. The inhibitory capabilities of acyclovir are highly selective due to the drug's strong affinity for _thymidine kinase_ (TK)[FDA label]. In summary, the antiviral effects of valacyclovir are achieved in 3 ways [FDA label]: 1) competitive inhibition of viral DNA polymerase 2) incorporation and termination of the growing viral DNA chain 3) inactivation of the viral DNA polymerase. The higher level of antiviral activity of acyclovir against HSV compared with VZV is attributed to its more efficient phosphorylation by viral thymidine kinase (TK).
TOXICITY
**LD50 Oral** Rat â 903.5 mg/kg [F3973] **Carcinogenesis, Mutagenesis, Impairment of Fertility** Valacyclovir was noncarcinogenic in lifetime carcinogenicity assays at single daily gavage doses of valacyclovir giving plasma acyclovir concentrations equivalent to human levels in the mouse bioassay and 1.4 to 2.3 times human levels in the rat bioassay. No clinically significant difference in the incidence of tumors between treated and control animals was observed, and valacyclovir was not found to shorten the latency period of tumors. Valacyclovir was tested in 5 genetic toxicity assays. An Ames assay was negative in the absence or presence of metabolic activation. An in vitro cytogenetic study with human lymphocytes and a rat cytogenetic study was negative [FDA label]. In the mouse lymphoma assay, valacyclovir was not found to be mutagenic without metabolic activation, however, in the presence of metabolic activation (76% to 88% conversion to acyclovir), valacyclovir was mutagenic. Valacyclovir was also found to be mutagenic in a mouse micronucleus assay [FDA label]. Valacyclovir did not impair fertility or reproduction in rats at 6 times the normal concentrations in human plasma [FDA label]. **Use in pregnancy** Valacyclovir is categorized as a pregnancy category B drug. There are insufficient well-controlled studies of valacyclovir in pregnant women. The general rate of birth defects in infants exposed to acyclovir in-utero is comparable to the rate for infants measured in the general population. This drug should be used during pregnancy only if the potential benefit justifies the possible fetal risk [FDA label]. **Use in nursing** Acyclovir, a major metabolite of valacyclovir, was excreted in breastmilk at lower concentrations when a normal therapeutic dose of valacyclovir was administered. Exercise caution when acyclovir is used while nursing [FDA label]. **A note on renal function and toxicity in elderly patients** Elderly patients and patients with decreased renal function are at increased risk of valacyclovir toxicity, which can sometimes lead to central nervous system effects, such as encephalopathy, agitation, dysarthria, mania, and psychosis, among other effects. Consider reducing the dose of this drug in these populations to decrease the risk of toxicity [FDA label].
MOA
Valacyclovir is the L-valine ester of aciclovir. It is classified as a nucleoside analog DNA polymerase enzyme inhibitor. Aciclovir is a purine (guanine) nucleoside analog is a metabolite that heavily contributes to the pharmacological actions of valacyclovir. In fact, most of valacyclovir's activity is attributed to acyclovir [A175885].; ; Valacyclovir is rapidly and almost completely converted in man to aciclovir and valine, likely by the enzyme _valacyclovir hydrolase_.; Aciclovir is a selective inhibitor of the herpes viruses, possessing in vitro activity against herpes simplex viruses (HSV) type 1 and type 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr Virus (EBV), as well as human herpesvirus 6 (HHV-6). Aciclovir has been shown to inhibit herpes virus DNA synthesis after it has been phosphorylated to the active triphosphate form [F3949].; ; The first stage of drug phosphorylation for acyclovir requires activation by a virus-specific enzyme. In the case of HSV, VZV and EBV this enzyme is the viral _thymidine kinase_ (TK), which is only found in virus-infected cells. The process of phosphorylation is completed (conversion from mono- to triphosphate) by cellular kinases. Acyclovir triphosphate competitively inhibits the virus DNA polymerase and incorporation of this agent results in DNA chain termination, stopping virus DNA synthesis and blocking virus replication [F3949]. The inhibitory capabilities of acyclovir are highly selective due to the drug's strong affinity for _thymidine kinase_ (TK)[FDA label].; ; ; In summary, the antiviral effects of valacyclovir are achieved in 3 ways [FDA label]: ; ; 1) competitive inhibition of viral DNA polymerase; ; 2) incorporation and termination of the growing viral DNA chain; ; 3) inactivation of the viral DNA polymerase. The higher level of antiviral activity of acyclovir against HSV compared with VZV is attributed to its more efficient phosphorylation by viral thymidine kinase (TK).
TOXICITY
**LD50 Oral** ; ; Rat â 903.5 mg/kg [F3973]; ; **Carcinogenesis, Mutagenesis, Impairment of Fertility**; ; Valacyclovir was noncarcinogenic in lifetime carcinogenicity assays at single daily gavage doses of valacyclovir giving plasma acyclovir concentrations equivalent to human levels in the mouse bioassay and 1.4 to 2.3 times human levels in the rat bioassay. No clinically significant difference in the incidence of tumors between treated and control animals was observed, and valacyclovir was not found to shorten the latency period of tumors. Valacyclovir was tested in 5 genetic toxicity assays. An Ames assay was negative in the absence or presence of metabolic activation. An in vitro cytogenetic study with human lymphocytes and a rat cytogenetic study was negative [FDA label].; ; In the mouse lymphoma assay, valacyclovir was not found to be mutagenic without metabolic activation, however, in the presence of metabolic activation (76% to 88% conversion to acyclovir), valacyclovir was mutagenic. Valacyclovir was also found to be mutagenic in a mouse micronucleus assay [FDA label]. ; ; Valacyclovir did not impair fertility or reproduction in rats at 6 times the normal concentrations in human plasma [FDA label]. ; ; **Use in pregnancy**; ; Valacyclovir is categorized as a pregnancy category B drug. There are insufficient well-controlled studies of valacyclovir in pregnant women. The general rate of birth defects in infants exposed to acyclovir in-utero is comparable to the rate for infants measured in the general population. This drug should be used during pregnancy only if the potential benefit justifies the possible fetal risk [FDA label].; ; **Use in nursing**; ; Acyclovir, a major metabolite of valacyclovir, was excreted in breastmilk at lower concentrations when a normal therapeutic dose of valacyclovir was administered. Exercise caution when acyclovir is used while nursing [FDA label]. ; ; ; **A note on renal function and toxicity in elderly patients**; ; Elderly patients and patients with decreased renal function are at increased risk of valacyclovir toxicity, which can sometimes lead to central nervous system effects, such as encephalopathy, agitation, dysarthria, mania, and psychosis, among other effects. Consider reducing the dose of this drug in these populations to decrease the risk of toxicity [FDA label].
DESCRIPTION
Valaciclovir is an antiviral drug used in the management of herpes simplex, herpes zoster, and herpes B.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
27
BOC Sciences Bioactive Compounds
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
Guide to Pharmacology
MedChem Express Bioactive Compound Library
Natural product-based probes and drugs
NIH Clinical Collections (NCC)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
87
Molecular Weight
324.15
Hydrogen Bond Acceptors
9
Hydrogen Bond Donors
3
Rotatable Bonds
7
Ring Count
2
Aromatic Ring Count
2
cLogP
-0.8
TPSA
151.14
Fraction CSP3
0.54
Chiral centers
1.0
Largest ring
6.0
QED
0.44
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
HSV
DNA polymerase
antibiotic
Bacterial
CMV
Pathway
Anti-infection
DNA Damage/DNA Repair
Indication
shingles, virus herpes simplex (HSV)
MOA
DNA polymerase inhibitor
Biosynthetic Origin
Nucleoside
Therapeutic Indication
Antiviral
Therapeutic Class
Antiviral Agents
Antiinfective Agents
Solubility
In vitro:<br/>10 mM in DMSO
Source data
