Everything about Acyclovir totally explained
| 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
| excretion =
Renal
| pregnancy_category = B3
(Au), B
(U.S.)
| legal_status = unscheduled/S4
(Au), POM
(UK)
| routes_of_administration =
Intravenous, oral, topical
}}
Aciclovir (
INN) or
acyclovir (
USAN, former
BAN), chemical name
acycloguanosine, is a
guanine analogue antiviral drug, marketed under trade names such as
Zovirax and
Zovir (
GSK). One of the most commonly-used antiviral drugs, it's primarily used for the treatment of
herpes simplex virus infections, 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's extremely selective and low in
cytotoxicity.
Pharmacologist Gertrude B. Elion was awarded the
1988 Nobel Prize in Medicine, partly for the development of acyclovir.
Pharmacology
Mechanism of action
Acylovir differs from previous
nucleoside analogues in that it contains only a partial
nucleoside structure: 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
phosphorylation than 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 can't 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's administered in an inactive (or less active form) and is metabolised into a more active species after administration.
Microbiology
Acylovir is active against most species in the
herpesvirus family. In descending order of 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 acyclovir hasn't 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.
Pharmacokinetics
Acylovir is poorly water soluble and has poor oral
bioavailability (10–20%), hence
intravenous administration is necessary if high concentrations are required. When orally administered, peak plasma concentration occurs after 1–2 hours. Acylovir has a high distribution rate, only 30% is protein-bound in plasma. The
elimination half-life of 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 Acylovir by esterases via hepatic
first-pass metabolism.
Clinical use
Indications
Acylovir is indicated for the treatment of HSV and VZV infections, including:
Genital herpes simplex (treatment and prophylaxis)
Herpes simplex labialis (cold sores)
Herpes zoster (shingles)
Acute chickenpox in immunocompromised patients
Herpes simplex encephalitis
Acute mucocutaneous HSV infections in immunocompromised patients
Herpes simplex keratitis (ocular herpes)
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.
Likewise oral therapy for episodes is inappropriate for most non-immunocompromised patients, whilst there's evidence for oral prophylactic role in preventing recurrences.
Dosage forms
Acyclovir is commonly marketed as tablets (200 mg, 400 mg and 800 mg), 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 effects
Systemic therapy
Common 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 necrolysis and/or anaphylaxis.Topical therapy
Acyclovir topical cream is commonly associated (≥1% of patients) with: dry or flaking skin and/or transient stinging/burning sensations. Infrequent adverse effects include erythema and/or itch.Toxicity
Since acyclovir can be incorporated also into the cellular DNA, it's a chromosome mutagen, therefore, its use should be avoided during pregnancy. However it hasn't been shown to cause any teratogenic nor carcinogenic effects. The acute toxicity (LD50) of aciclovir when given orally is greater than 1 g/kg, due to the low oral bioavailability.
Footnotes
Further Information
Get more info on 'Acyclovir'.
|
External Link Exchanges
Do you know how hard it is to get a link from a large encyclopaedia? Well we're different and will prove it. To get a link from us just add the following HTML to your site on a relevant page:
<a href="http://aciclovir.totallyexplained.com">Aciclovir Totally Explained</a>
Then simply click through this link from your web page. Our crawlers will verify your link, extract the title of your web page and instantly add a link back to it. If you like you can remove the words Totally Explained and embed the link in article text.
As long as your link remains in place, we'll keep our link to you right here. Please play fair - our crawlers are watching. Your site must be closely related to this one's topic. Any kind of spamming, dubious practises or removing the link will result in your link from us being dropped and, potentially, your whole site being banned. |
