Indications
Acyclovir is a versatile antiviral medication indicated for a variety of herpes-related conditions. Topical acyclovir cream is prescribed for the management of recurrent herpes labialis in immunocompetent individuals aged 12 and older. Additionally, oral formulations such as tablets, capsules, and suspensions are employed to treat conditions like herpes zoster, genital herpes, and chickenpox. The topical ointment variant is recommended for initial genital herpes and limited non-life-threatening mucocutaneous herpes simplex infections in immunocompromised patients. Acyclovir cream combined with hydrocortisone serves to treat recurrent herpes labialis and expedite lesion healing in patients 6 years and older. The buccal tablet format specifically addresses recurrent herpes labialis, and the ophthalmic ointment is indicated for acute herpetic keratitis.
Pharmacodynamics
The pharmacodynamic action of acyclovir is based on its role as a deoxynucleoside analog. This mechanism effectively inhibits viral DNA polymerase, thereby disrupting DNA replication in various herpesviruses. Acyclovir boasts a broad therapeutic window, with overdose occurrences being rare among healthy individuals.
Absorption
Acyclovir's oral bioavailability ranges between 10-20% and tends to diminish with higher dosages, yet is unaffected by the presence of food. Topically applied formulations, such as ointments, demonstrate an absorption rate of less than 0.02-9.4%. Minimal absorption is observed with buccal tablets and ophthalmic ointments. Key pharmacokinetic parameters of oral acyclovir reveal a mean time to maximum concentration (Tmax) of 1.1±0.4 hours, a peak plasma concentration (Cmax) between 593.7-656.5 ng/mL, and an area under the curve (AUC) ranging from 2956.6-3102.5 h/ng/mL.
Metabolism
The metabolic pathway of acyclovir involves less than 15% conversion to 9-carboxymethoxymethylguanine via alcohol dehydrogenase and aldehyde dehydrogenase, and around 1% transformation to 8-hydroxy-acyclovir by aldehyde oxidase. Acyclovir is phosphorylated to acyclovir monophosphate by viral thymidine kinase. This monophosphate form is subsequently converted to acyclovir diphosphate through guanylate kinase and further to acyclovir triphosphate by multiple enzymes, including nucleoside diphosphate kinase, pyruvate kinase, creatine kinase, and others.
Mechanism of Action
Acyclovir exerts its antiviral effects through a series of enzymatic conversions that begin with its phosphorylation by viral thymidine kinase, resulting in the formation of acyclovir monophosphate. This compound is subsequently converted into acyclovir diphosphate by guanylate kinase. Further phosphorylation by enzymes such as nucleoside diphosphate kinase, pyruvate kinase, and others, leads to the production of acyclovir triphosphate. This triphosphate form has a higher affinity for viral DNA polymerase compared to cellular DNA polymerase, allowing it to integrate into viral DNA. The absence of the 2' and 3' carbons in the acyclovir structure causes premature DNA chain termination. Additionally, acyclovir triphosphate can bind so effectively to viral DNA polymerase that it prevents other bases from associating, subsequently inactivating the enzyme.
