IUPAC_name = 2-amino-9-((2-hydroxyethoxy)methyl)-1H-purin-6(9H)-one
synonyms = acycloguanosine
CAS_number = 59277-89-3
ChemSpiderID = 1945
ATC_prefix = J05
ATC_suffix = AB01
ATC_supplemental = ATC|D06|BB03 ATC|S01|AD03
PubChem = 2022
DrugBank = APRD00567
C=8 | H=11 | N=5 | O=3
molecular_weight = 225.21 g/mol
melting_point = 256.5
bioavailability = 10–20% (oral)
protein_bound = 9–33%
metabolism = Viral thymidine kinase
elimination_half-life = 2.2–20 hours
pregnancy_category = B3 (Au), B (U.S.)
legal_status = unscheduled/S4 (Au), POM (UK)
routes_of_administration = Intravenous, oral, topical
Aciclovir (INN) (pronEng|eɪˈsaɪkloʊvɪr) or acyclovir (USAN, former BAN), chemical name acycloguanosine, is a
guanosineanalogue antiviral drug, marketed under trade names such as "Cyclovir", "Herpex", "Acivir", "Zovirax" and "Zovir" (GSK). One of the most commonly-used antiviral drugs, it is primarily used for the treatment of herpes simplex virusinfections, as well as in the treatment of herpes zoster (shingles).
Aciclovir was seen as the start of a new era in antiviral therapy, as it is extremely selective and low in
cytotoxicity. Pharmacologist Gertrude B. Elionwas awarded the 1988Nobel Prize in Medicine, partly for the development of aciclovir.
Mechanism of action
Aciclovir differs from previous
nucleoside analoguesin that it contains only a partial nucleosidestructure: the sugar ring is replaced by an open-chain structure. It is selectively converted into acyclo- guanosine monophosphate(acyclo-GMP) by viral thymidine kinase, which is far more effective (3000 times) in phosphorylationthan cellular thymidine kinase. Subsequently, the "monophosphate" form is further phosphorylated into the active "triphosphate" form, acyclo- guanosine triphosphate(acyclo-GTP), by cellular kinases. Acyclo-GTP is a very potent inhibitor of viral DNA polymerase; it has approximately 100 times greater affinity for viral than cellular polymerase. As a substrate, acyclo-GMP is incorporated into viral DNA, resulting in chain termination. It has also been shown that viral enzymes cannot remove acyclo-GMP from the chain, which results in inhibition of further activity of DNA polymerase. Acyclo-GTP is fairly rapidly metabolised within the cell, possibly by cellular phosphatases.
In sum, aciclovir can be considered a
prodrug: it is administered in an inactive (or less active form) and is metabolised into a more active species after administration.
Aciclovir is active against most species in the
herpesvirusfamily. In descending order of activity:O'Brien JJ, Campoli-Richards DM. Aciclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1989;37(3):233-309. PMID 2653790]
Herpes simplex virustype I (HSV-1)
*Herpes simplex virus type II (HSV-2)
Varicella zoster virus(VZV)
Cytomegalovirus(CMV) -- least activity
Activity is predominantly 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 aciclovir 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.Sweetman S, editor. Martindale: The complete drug reference. 34th ed. London: Pharmaceutical Press; 2004. ISBN 0-85369-550-4]
Aciclovir is poorly water soluble and has poor oral
bioavailability(10–20%), hence intravenousadministration is necessary if high concentrations are required. When orally administered, peak plasma concentration occurs after 1–2 hours. Aciclovir has a high distribution rate, only 30% is protein-bound in plasma. The elimination half-lifeof aciclovir is approximately 3 hours. It is renally excreted, partly by glomerular filtration and partly by tubular secretion.
The poor oral bioavailability may also be improved by administering
Valaciclovir, which has a oral bioavailability of about 55%. Valaciclovir is then converted to Aciclovir by esterases via hepatic first-pass metabolism.
Aciclovir is indicated for the treatment of HSV and VZV infections, including:Rossi S, editor.
Australian Medicines Handbook2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3]
herpes simplex(treatment and prophylaxis)
* Herpes simplex labialis (
chickenpoxin immunocompromised patients
Herpes simplex encephalitis
* Acute mucocutaneous HSV infections in immunocompromised patients
* Herpes simplex
* Herpes simplex
blepharitis(not to be mistaken with ocular herpes)
* Bell's Palsy
It has been claimed that the evidence for the effectiveness of topically applied cream for recurrent labial outbreaks is weak. [cite journal
title=Evidence for efficacy of topical aciclovir in recurrent herpes labialis is weak
journal=BMJ | year=1996 | month=6 Jul | volume=313 | pages=46
url=http://www.bmj.com/cgi/content/full/313/7048/46/a - Letter] An earlier review of scientific literature showed that there is some effect in reducing the number and duration of lesions if aciclovir is applied at an early stage of an outbreak. [cite journal | author=Graham Worrall | title=Acyclovir in recurrent herpes labialis | journal=BMJ | year=1996 | month=6 Jan | volume=312 | pages=6 | url=http://www.bmj.com/cgi/content/full/312/7022/6 | pmid=8555890 - Editorial] However, it was concluded that oral therapy for episodes is inappropriate for most non-immunocompromised patients based on costs and benefits, presumably in countries where aciclovir is only available on prescription. It was concluded that there is evidence for an oral prophylactic role in preventing recurrences.
Aciclovir is commonly marketed as tablets (200mg, 400mg, 800mg and 1 gram), topical cream (5%), intravenous injection (25 mg/mL) and ophthalmic ointment (3%). Cream preparations are used primarily for labial herpes simplex. The intravenous injection is used when high concentrations of aciclovir are required. The ophthalmic ointment preparation is only used for herpes simplex keratitis.
adverse drug reactions (≥1% of patients) associated with systemic acyclovir therapy (oral or IV) include: nausea, vomiting, diarrhea and/or headache. In high doses, hallucinations have been reported. Infrequent adverse effects (0.1–1% of patients) include: agitation, vertigo, confusion, dizziness, oedema, arthralgia, sore throat, constipation, abdominal pain, rash and/or weakness. Rare adverse effects (<0.1% of patients) include: coma, seizures, neutropenia, leukopenia, crystalluria, anorexia, fatigue, hepatitis, Stevens-Johnson syndrome, toxic epidermal necrolysisand/or anaphylaxis.
Additional common adverse effects, when acyclovir is administered IV, include
encephalopathy(1% of patients) and injection site reactions. The injection formulation is alkaline( pH11), and extravasationmay cause local tissue pain and irritation. Renal impairment has been reported when acyclovir is given in large, fast doses intravenously, due to the crystallisation of acyclovir in the kidneys.
When applied to the eye, acyclovir is commonly associated (≥1% of patients) with transient mild stinging. Infrequently (0.1–1% of patients), ophthalmic aciclovir is associated with superficial
punctate keratitisand/or allergic reactions.
Since acyclovir can also be incorporated into cellular
DNA, it is a chromosome mutagen, therefore, its use should be avoided during pregnancy. Fact|date=May 2008 However it has not been shown to cause any teratogenic or carcinogenic effects. Fact|date=May 2008 The acute toxicity (LD50) of aciclovir when given orally is greater than 1 g/kg, due to its low oral bioavailability. Fact|date=May 2008
* Harvey Stewart C. in Remington’s Pharmaceutical Sciences 18th edition: (ed. Gennard, Alfonso R.) Mack Publishing Company, 1990. ISBN 0-912734-04-3.
* Huovinen P., Valtonen V. in Kliininen Farmakologia (ed. Neuvonen et al.). Kandidaattikustannus Oy, 1994. ISBN 951-8951-09-8.
* Périgaud C., Gosselin G., Imbach J. -L.: Nucleoside analogues as chemotherapeutic agents: a review. Nucleosides and nucleotides 1992; 11(2-4)
* Rang H.P., Dale M.M., Ritter J.M.: Pharmacology, 3rd edition. Pearson Professional Ltd, 1995. 2003 (5th) edition ISBN 0-443-07145-4; 2001 (4th) edition ISBN 0-443-06574-8; 1990 edition ISBN 0-443-03407-9.
Wikimedia Foundation. 2010.
Look at other dictionaries:
Aciclovir — Nombre (IUPAC) sistemático 2 amino 9 (2 hidroxietoximetil) 3H purin 6 ona … Wikipedia Español
Aciclovir — Général Nom IUPAC 2 amino 9 ((2 hydroxyethoxy)methyl) 1H purin 6(9H) one Synonymes … Wikipédia en Français
aciclovir — nucleósido sintético con propiedades antivíricas frente a virus herpes tipos 1 y 2, virus de la varicela, virus de Epstein Barr y citomegalovirus. estructura química [véase http://www.iqb.es/diccio/a/ac.htm#aciclovir] monografía [véase http://www … Diccionario médico
Aciclovir — ● Aciclovir nom masculin (nom déposé) Médicament antiviral utilisé dans les infections dues au virus de l herpès et aux virus varicelle zona … Encyclopédie Universelle
Aciclovir — Strukturformel Allgemeines Freiname Aciclovir Andere Name … Deutsch Wikipedia
Aciclovir — АЦИКЛОВИР ( Аciclovir ). 9 (2 Гидрокси)этоксиметилгуанин, или 2 амино 1,9 дигидро 9 (2 гидрокси) этоксиметил 6Н пурин 6 он. Синонимы: Виролекс, Зовиракс, Асусloguanosine, Acyclovir, Cycloviran, Milavir, Virolex. Противовируcный препарат, особенно … Словарь медицинских препаратов
Aciclovir — … Википедия
aciclovir — Eng. Acyclovir Antivírico análogo de la guanosina que inhibe la DNA polimerasa de los virus herpers simple tipo I y II y varicela zóster, siendo sus principales indicaciones en Oftalmología la úlcera corneal herpética y el herpes zóster de la… … Diccionario de oftalmología
Aciclovir — A|ci|c|lo|vir [Kunstw.], das; s: internat. Freiname für ein als Virostatikum wirkendes Nukleosid Antibiotikum … Universal-Lexikon
aciclovir — (acyclovir) n. an antiviral drug that inhibits DNA synthesis in cells infected by herpesvirus. Administered topically, by mouth, or intravenously, it is used in the treatment of herpes zoster, genital herpes, herpetic eye disease, and herpes… … Medical dictionary