Chemicals / Complex Chemical Agents/ Chemical:
Acyclovir

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In Europe the prescription cascade must be followed. In the USA FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
Antiviral drug active against Herpesvirus hominis 1, Herpesvirus hominis 2 and varicella-zoster virus.

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Names and Formulae
Type 2'-deoxyguanosine analogue. (B567.99.w99)
Alternative Names Aciclovir, ACV, 9-(2-hydroxyethoxymethyl)guanine, Zovirax, acyloguanosine. (B135.49.w49, B553.44.w44, B567.99.w99)
Chemical Formula --
Chemical Structure --
Molecular Weight --
Related Chemicals
  • Acyclovir is an analogue of 2'-deoxyguanosine. (J222.340.w1)
  • Valacyclovir is the L-valine ester of acyclovir which is given orally as a prodrug which is then converted to acyclovir in the body. (J549.30.w1)

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Physical Properties / Chemistry
Appearance

White crystalline solid. (B567.99.w99)

Melting point --
Boiling point --
Density --
Water solubility 3 mg/mL at 25 C. (B567.99.w99)

Sodium salt: more than 100 mg/mL at 25 C. (B567.99.w99)

Other solubility --
Acid/Base Acidic ionization constant 2.27; basic ionization constant 9.25. (B567.99.w99)

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Pharmacology & General Information
Pharmacology
  • Acyclovir is phosphorylated in cells infected with herpes simplex virus or varicella-zoster virus. The first phosphorylation step is carried out by a thymidine kinase specific to these viruses, following which the second and third phosphorylations are carried out by cellular enzymes. (B135.49.w49, B567.99.w99)
    • Phosphorylation by viral thymidine kinase is 30 - 100 times as fast as phosphorylation by host cell kinase. (B135.49.w49, B560.14.w14)
  • Acyclovir triple phosphate is a potent alternative-substrate inhibitor, competing with dGTP (deoxyguanosine triphosphate) to be bound to the herpesvirus DNA polymerase and incorporated into viral DNA. One incorporated, viral DNA-polymerase-associated 3'-exonuclease is unable to excise the drug, and the viral polymerase cannot add another deoxyribonucleoside triphosphate onto the chain following acyclovir because the acyclovir does not have a 3'-hydroxyl. (B560.14.w14) therefore the chain is terminated (viral DNA production is stopped). (B560.14.w14, B567.99.w99)
  • Additionally, it is possible for the DNA polymerase plus a deoxynriboucleoside triphosphate to become trapped in a reversible dead-end complex with the acyclovir-terminated primer. (B560.14.w14, B567.99.w99)
    • Acyclovir triphosphate inhibits herpesvirus DNA polymerase 10 - 30 times more than it inhibits host cell DNA polymerase. B567.99.w99
  • This is an analogue of 2'-deoxyguanosine. It is active following metabolism to acyclovir triphosphate. The first phosphorylation step is catalysed by thymidine kinase in HSV-infected (and VZV-infected) cells, while the second and third phosphorylation steps are catalysed by cellular enzyme. Acyclovir triphosphate competes with 2'-deoxyguanosine triphosphate as a substrate for viral DNA polymerase and is inserted into the replicating viral DNA; synthesis of the viral DNA then stops. (J222.340.w1)
Storage / Stability --
Legal Category (In UK) --

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne MA VetMB PhD MRCVS (V.w5)
Referees Suzanne I. Boardman (V.w6)

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Therapeutic Information

Uses/Indications
Activity
  • Potently active against herpes simplex virus Type 1, herpes simplex virus type 2 and varicella zoster virus. (B567.99.w99)
  • Moderately active against Herpes simiae (B virus). (B567.99.w99)
  • Limited activity against human cytomegalovirus. (B567.99.w99)
Appropriate Use
  • In the treatment of herpes simplex and varicella-zoster virus infections. 

Humans

  • In the treatment/suppression of mucocutaneous herpes simplex infections in immunocompromised individuals. (B567.99.w99)
  • Treatment of initial/recurrent genital herpes infections, and chronic suppression of infection in individuals with frequent recurrent genital herpes. (B567.99.w99)
  • Treatment of varicella-zoster infection (in immunocompetent and immunosuppressed individuals). (B567.99.w99)
  • Treatment of herpes simplex encephalitis. (B567.99.w99)
  • Treatment of herpes zoster. (B567.99.w99)
  • Less effective in the treatment of Epstein-Barr virus or cytomegalovirus. (B553.44.w44)

In psittacines: 

Used experimentally; decreased mortality following herpesvirus infection, if given before the onset of clinical signs. (B553.44.w44) 

Limitations
  • Reduced activity against viral mutants with either:
    • Reduced virus-specific thymidine kinase. Occurs in vivo in patients with very poor endogenous immunity recieving prolonged courses of acyclovir. (B567.99.w99)
    • Altered DNA polymerase with a lower binding affinity to acyclovir triphosphate. Very rare in vivo. (B567.99.w99)
Notes --

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Pharmacokinetics and Drug Interactions
Absorption / Bioavailability
  • About 20% (based on an oral dose of 200 mg in humans). (B567.99.w99)
  • 15 - 30%; may decrease with increasing dose. (B553.44.w44)
  • Oral bioavailability is 10-20%. (J222.340.w1)
Distribution
  • "Volume of distribution approximates total body water." (B553.44.w44)
  • Concentrations of acyclovir in CSF and in aqueous humour are about a third to one-half those in plasma. B553.44.w44
Plasma Protein binding / Storage
  • Low - about 22 - 33%; (B567.99.w99) 9 - 33%. (B553.44.w44)
Elimination Route
  • Mainly via the kidneys, as unchanged drug (71 - 99% excreted in urine, human studies with labelled drug). (B567.99.w99)
    • Excreted by glomerular filtration and tubular excretion, as indicated by a higher renal clearance than occurs for creatinine. (B567.99.w99)
  • Some metabolism: following intravenous dosing, about 10% of the dose was converted to the metabolite 9-carboxymethoxymethylguanine and about 2% to the metabolite 8-hydroxy-9-(2-hydroxyethoxymethyl)-guanine. (B567.99.w99)
Elimination half-life / Clearance Rate
  • In humans with normal renal function, average total body clearance about 300 mL/minute/1.73 m; terminal half-life about 3.0 hours. (B567.99.w99)
  • Plasma half-life 2-3 hours (J222.340.w1); 2.5 - 3.5 hours. (B553.44.w44)
    • Intracellular half-life of the triphosphate is 1 - 2 hours (in vitro data). (J222.340.w1)
  • Note: in humans with chronic renal failure, average total body clearance about 29 mL/minute/1.73 m; terminal half-life about 19.0 hours. (B567.99.w99)
Drug Interactions --

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Administration
Formulations available Human formulations
  • Sterile powder to be reconstituted for intravenous use. (B135.49.w49, B567.99.w99)
  • 200 mg capsule. (B135.49.w49, B567.99.w99)
  • 400 mg tablets, 800 mg tablets. (B135.49.w49, B567.99.w99)
  • 200 mg/5 mL oral suspension. (B135.49.w49, B567.99.w99)
  • 5% topical (non-ophthalmic) ointment. (B567.99.w99)
  • 3% ophthalmic ointment. (B567.99.w99)
Doses / Administration Routes / Frequencies --
  • Note: reduced dosages may be required in individuals with renal impairment, in whom the drug may accumulate. (B567.99.w99)
Monitoring parameters --

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Withdrawal period / Withholding time
Notes --

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Contraindicated in individuals showing hypersensitivity to the drug or to components in its formulation. (B567.99.w99)
Adverse Effects / Side Effects / Warnings
  • Adverse effects in humans include:
    • Reversible nephropathy due to crystallisation of the drug in the renal tubules. This normally occurs only after intravenous administration. It is uncommon and can be managed by giving fluids at 1 litre per gram of acyclovir, infusing the dose at a rate of no more than 6 mg/mL, over one hour, and reducing the dose in individuals with renal insufficiency (as indicated by creatinine clearance). (J222.340.w1)
    • Gastrointestinal disturbance. This is an uncommon direct effect of the drug and can be managed by reducing the drug dose if necessary. (J222.340.w1)
    • Irritation at the site of injection; phlebitis. (B553.44.w44, J222.340.w1)
      • Due to the high pH of the drug in solution (pH 11). Prevented by ensuring the drug is given intravenously, without extravasation. (J222.340.w1)
    • Rash as a rare idiosyncratic reaction. If moderate to severe, it may be necessary to discontinue the drug. (J222.340.w1)
    • Encephalopathy as a rare reaction precipitated by renal failure or by other drugs with adverse effects on the CNS. Treated by discontinuing use of the drug. (J222.340.w1)
Operator Warnings --
Overdose / Acute Toxicity --

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Detailed Toxicological Information
Classification --
Acute Toxicity
  • Little toxicity to human cells not infected with one of the herpesviruses. (B567.99.w99)
Chronic Toxicity --
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Sources in the Environment
Natural sources --
Human-associated sources

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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