Advertisement

History, pharmacokinetics, and pharmacology of acyclovir

  • Dannie H. King
    Correspondence
    Reprint requests to: Dannie H. King, Ph.D., Vice President, Research and Development, Oclassen Pharmaceuticals, 201 Tamal Vista Blvd., Corte Madera, CA 94925.
    Affiliations
    From the Department of Infectious Diseases, Burroughs Wellcome Company.
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      A screening program for antiviral drugs begun at Burroughs Wellcome in the 1960s resulted in the discovery of acyclovir in 1974. Preclinical investigation brought the drug to clinical trials in 1977 and the first form of the drug (topical) was available to physicians in 1982. Activity of acyclovir is greatest against herpes 1 and herpes 2, less against varicella zoster, still less against Epstein-Barr, and very little against cytomegalovirus. Acyclovir is an antiviral agent only after it is phosphorylated in infected cells by a viral-induced thymidine kinase. Acyclovir monophosphate is phosphorylated to diphosphate and triphosphate forms by cellular enzymes in the infected host cell where the drug is concentrated. Acyclovir triphosphate inactivates viral deoxyribonucleic acid polymerase. Acyclovir incorporation into the growing viral deoxyribonucleic acid chain causes its termination. The antiviral process has relatively little effect on normal, uninfected cells. An important toxic effect of acyclovir is its potential to cause obstructive nephropathy. The drug is excreted primarily by the kidney, which may require smaller doses in patients with decreased kidney function. Oral dosages of acyclovir as recommended for herpes simplex are probably not adequate for varicella zoster infections.
      To read this article in full you will need to make a payment
      AAD Member Login
      AAD Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Schaeffer HJ
        • Beauchamp L
        • de Miranda P
        • Elion GB
        • Bauer DJ
        • Collins P
        9-(2-Hydroxyethoxymethyl) guanine activity against viruses of the herpes group.
        Nature. 1978; 272: 583-585
        • Schaeffer HJ
        Acyclovir chemistry and spectrum of activity.
        Am J Med. 1982; 73: 4-6
        • Elion GB
        • Furman TA
        • Fyfe JA
        • de Miranda P
        • Beauchamp L
        • Schaeffer HJ
        Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine.
        Proc Natl Acad Sci USA. 1977; 74: 5716-57120
        • Elion GB
        Mechanism of action and selectivity of acyclovir.
        Am J Med. 1982; 73: 7-13
        • Elion GB
        The biochemistry and mechanism of action of acyclovir.
        J Antimicrob Chemother. 1983; 12: 9-17
        • McGuirt PV
        • Furman PA
        • Acyclovir inhibition of viial DNA
        chain elongation in herpes simplex virus-infected cells.
        Am J Med. 1982; 73: 67-71
        • de Miranda P
        • Krasny HC
        • Page DA
        • Elion GB
        The disposition of acyclovir in different species.
        J Pharmacol Exp Ther. 1981; 219: 309-315
        • de Miranda P
        • Krasny HC
        • Page DA
        • Elion GD
        Species differences in the disposition of acyclovir.
        Am J Med. 1982; 73: 31-35
        • de Miranda P
        • Blum MR
        Pharmacokinetics of acyclovir after intravenous and oral administration.
        J Antimicrob Chemother. 1983; 12: 29-37
        • Stanberry LR
        • Kern ER
        • Richards JT
        • Abbott TM
        • Overall Jr, JC
        Genital herpes in guinea pigs: pathogenesis of the primary infection and description of recurrent disease.
        J Infect Dis. 1982; 146: 397-404
        • Pronovost AD
        • Lucia HL
        • Dann PR
        • Hsiung GD
        Effect of acyclovir on genital herpes in guinea pigs.
        J Infect Dis. 1982; 145: 904-908
        • Tucker WE
        • Johnson RE
        • Macklin AW
        • et al.
        Preclinical toxicology studies with acyclovir: ophthalmic and cutaneous tests.
        Fundam Appl Toxicol. 1983; 3: 569-572
        • Tucker WE
        • Macklin AW
        • Szot RJ
        • et al.
        Preclinical toxicology studies with acyclovir: acute and subchronic tests.
        Fundam Appl Toxicol. 1983; 3: 573-578
        • Tucker WE
        • Krasny HC
        • de Miranda P
        • et al.
        Preclinical toxicology studies with acyclovir: carcinogenicity bioassays and chronic toxicity tests.
        Fundam Appl Toxicol. 1983; 3: 579-586