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Integration of Pharmaceutical Discovery and Development pp 313–344Cite as

Famciclovir

Discovery and Development of a Novel Antiherpesvirus Agent

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Part of the book series: Pharmaceutical Biotechnology ((PBIO,volume 11))

Conclusion

Penciclovir is a highly selective antiviral agent with a prolonged mechanism of action against members of the herpesvirus family and against HBV. In the discovery phase, biochemical mode of action studies identified key differences to the existing therapy, acyclovir, which impacted the strategy of the subsequent clinical evaluation. A key issue for the research program was the identification of a suitable orally bioavailable prodrug. In addition to oral bioavailability studies in animals, studies of metabolism in human tissue and body fluids played a crucial role in the choice of the preferred prodrug, famciclovir. Clinical evaluation of the human pharmacokinetics of famciclovir fully confirmed its utility for the oral delivery of penciclovir. The good blood levels of penciclovir from oral administration of famciclovir combined with the prolonged mechanism of action result in a clinically effective agent with significant reductions in both size and frequency of dose relative to previously available therapy. Overall, an early and prolonged interaction of the research program with the needs of development, clinical investigators, and regulatory authorities greatly influenced the progression of penciclovir and famciclovir into clinical usage.

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References

  • Ahmed, A., and Wooley, P. D., 1996, Comparison of famciclovir and aciclovir in first episode genital herpes: Possible clinical effect on latency (abstract), European Congress on STDs, Paris.

    Google Scholar 

  • Ashton, R. J., Abbott, K. H., Smith, G. M., and Sutton, D., 1994, Antiviral activity of famciclovir and acyclovir in mice infected intraperitoneally with herpes simplex virus type 1 SC16, J. Antimicrob. Chemother. 34:287–290.

    CAS  PubMed  Google Scholar 

  • Bacon, T. H., 1996, Famciclovir, from the bench to the patient—A comprehensive review of preclinical data, Int. J. Antimicrob. Agents 7:119–134.

    CAS  Google Scholar 

  • Bacon, T. H., and Boyd, M. R., 1995, Activity of penciclovir against Epstein-Barr virus, Antimicrob. Agents Chemother. 39:1599–1602.

    CAS  PubMed  Google Scholar 

  • Bacon, T. H., and Howard, B. A., 1996, Further characterisation of the inhibition of herpes simplex virus replication in human cell lines by penciclovir and aciclovir, Antiviral Chem. Chemother. 7:128–137.

    CAS  Google Scholar 

  • Bacon, T. H., and Schinazi, R. F., 1993, An overview of the further evaluation of penciclovir against herpes simplex virus and varicella-zoster virus in cell culture highlighting contrasts with acyclovir, Antiviral Chem. Chemother. 4(Suppl. l):25–36.

    CAS  Google Scholar 

  • Bacon, T. H., Gilbart, J., Howard, B. A., and Standring-Cox, R., 1996a, Inhibition of varicella-zoster virus by penciclovir in cell culture and mechanism of action, Antiviral Chem. Chemother. 7:71–78.

    CAS  Google Scholar 

  • Bacon, T. H., Howard, B. A., Spender, L. C., and Boyd, M. R., 1996b, Activity of penciclovir in antiviral assays against herpes simplex virus, J. Antimicrob. Chemother. 37:303–313.

    CAS  PubMed  Google Scholar 

  • Bailey, S., and Harnden, M. R., 1988, Analogues of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbuty 1)guanine. Part 2. Substitutions on C-1′ and C-3′ of the acyclic N-9 substituent, J. Chem. Sot: Perkin Trans. 1 1988:2767–2775.

    Google Scholar 

  • Bebault, G. M., Wall, R. A., Ronnie, B. A., and Sacks, S. L., 1995, Penciclovir (PCV) triphosphate (PCVTP) and acyclovir (ACV) triphosphate (ACVTP) in a human schwannoma continuous cell line (SW) infected with varicella zoster virus (VZV), Can. J. Infect. Dis. 6(Suppl. C):287C.

    Google Scholar 

  • Boker, K. H., Ringe, B., Krüger, M., Pichlmayr, R., and Manns, P., 1994, Prostaglandin E plus famciclovir—A new concept for the treatment of severe hepatitis B after liver transplantation. Transplantation 57:1706–1708.

    CAS  PubMed  Google Scholar 

  • Boyd, M. R., Bacon, T. H., Sutton, D., and Cole, M., 1987, Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine (BRL 39123) in cell culture, Antimicrob. Agents Chemother. 31:1238–1242.

    CAS  PubMed  Google Scholar 

  • Boyd, M. R., Bacon, T. H., and Sutton, D., 1988a, Antiherpesvirus activity of 9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine (BRL 39123) in animals, Antimicrob. Agents Chemother. 32:358–363.

    CAS  PubMed  Google Scholar 

  • Boyd, M. R., Boon, R., Fowles, S. E., Pagano K., Sutton, D., Vere Hodge, R. A., and Zussman, B. D., 1988b, Some biological properties of BRL 42810, a well absorbed oral prodrug of the antiherpes virus agent BRL 39123, Antiviral Res. 9:146

    Google Scholar 

  • Boyd, M. R., Safrin, S., and Kern, E. R., 1993, Penciclovir: A review of its spectrum of activity, selectivity and cross-resistance pattern, Antiviral Chem. Chemother. 4(Suppl. I):3–11.

    CAS  Google Scholar 

  • Carrington, D., 1996, Reducing the duration of zoster-associated pain with famciclovir (abstract), in: First European Congress of Chemotherapy, Glasgow.

    Google Scholar 

  • Chiou, H. C., Kumura, K., Hu, A., Kerns, K. M., and Coen, D. M., 1995, Penciclovir-resistance mutations in the herpes simplex virus DNA polymerase gene, Antiviral Chem. Chemother. 6:281–288.

    CAS  Google Scholar 

  • Clarke, S. E., Harrell, A. W., and Chenery, R. J., 1995, The role of aldehyde oxidase in the in vitro conversion of famciclovir to penciclovir in human liver. Drug Metab. Dispos. 23:251–254.

    CAS  PubMed  Google Scholar 

  • Daniels, S., and Schentag, J. J., 1993, Drug interaction studies and safety of famciclovir in healthy volunteers: A review, Antiviral Chem. Chemother. 4(Suppl. l):57–64.

    CAS  Google Scholar 

  • Dannaoui, E., Trépo, C., and Zoulim, F., 1997, Inhibitory effect of penciclovir-triphosphate on duck hepatitis B virus reverse transcription, Antimicrob. Agents Chemother. 8:38–46.

    CAS  Google Scholar 

  • Datema, R., Ericson, A.-C., Field, H. J., Larsson, A., and Stenberg, K., 1987, Critical determinants of antiherpes efficacy of buciclovir and related acyclic guanosine analogs, Antiviral Res. 7:303–316.

    Article  CAS  PubMed  Google Scholar 

  • Degreef, H., and Famciclovir Herpes Zoster Clinical Study Group, 1994, Famciclovir, a new oral antiherpes drug: Results of the first controlled clinical study demonstrating its efficacy and safety in the treatment of uncomplicated herpes zoster in immunocompetent patients. Int. J. Antimicrob. Agents 4:241–246.

    CAS  Google Scholar 

  • de Miranda, P., and Blum, M. R., 1983, Pharmacokinetics of acyclovir after intravenous and oral administration, J. Antimicrob. Chemother. 12(Suppl. B):29–37.

    PubMed  Google Scholar 

  • de Miranda, P., and Good, S. S., 1992, Species differences in the metabolism and disposition of antiviral nucleoside analogues: 1. Acyclovir, Antiviral Chem. Chemother. 3:1–8.

    Google Scholar 

  • de Miranda, P., Krasny, H. C., Page, D. A., and Elion, G. B., 1981, The disposition of acyclovir in different species, J. Pharmacol. Exp. Ther. 219:309–315.

    PubMed  Google Scholar 

  • Diaz-Mitoma, F., Sibbald, R. G., Shafran, S. D., and the Collaborative Famciclovir Genital Herpes Suppression Group, 1996, Famciclovir suppression of recurrent genital herpes, in: Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, American Society for Microbiology.

    Google Scholar 

  • Earnshaw, D. L., and Vere Hodge, R. A., 1992, Effective inhibition of herpesvirus DNA synthesis by (S)-penciclovir-triphosphate, in: Program and Abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, American Society for Microbiology.

    Google Scholar 

  • Earnshaw, D. L., Bacon, T. H., Darlison, S. J., Edmonds, K., Perkins, R. M., and Vere Hodge, R. A., 1992, Mode of antiviral action of penciclovir in MRC-5 cells infected with herpes simplex virus type 1 (HSV-1), HSV-2 and varicella-zoster virus, Antimicrob. Agents Chemother. 36:2747–2757.

    CAS  PubMed  Google Scholar 

  • Ertl, P., Snowden, W., Lowe, D., Miller, W., Collins, P., and Littler, E., 1995, A comparative study of the in vitro and in vivo antiviral activities of acyclovir and penciclovir. Antiviral Chem. Chemother. 6:89–97.

    CAS  Google Scholar 

  • Field, H. J., and Thackray, A. M., 1995, The effects of delayed-onset chemotherapy using famciclovir or valaciclovir in a murine immunosuppression model for HSV-1, Antiviral Chem. Chemother. 6:210–216.

    CAS  Google Scholar 

  • Field, H. J., Tewari, D., Sutton, D., and Thackray, A. M., 1995, Comparison of efficacies of famciclovir and valaciclovir against herpes simplex virus type 1 in a murine immunosuppression model, Antimicrob. Agents Chemother. 39:1114–1119.

    CAS  PubMed  Google Scholar 

  • Fowles, S. E., Pierce, D. M., Prince, W. T, and Thow, J. C., 1990, Effect of food on the bioavailability and pharmacokinetics of penciclovir, a novel antiherpes agent, following oral administration of the pro-drug, famciclovir, Br. J. Clin. Pharmacol. 29:620P–621P.

    Google Scholar 

  • Fowles, S. E., Fairless, A. J., Pierce, D. M., and Prince, W. T, 1991, A further study on the effect of food on the bioavailability and pharmacokinetics of penciclovir after oral administration of famciclovir, Br. J. Clin. Pharmacol. 32:657P.

    Google Scholar 

  • Fowles, S. E., Pierce, D. M., Prince, W. T., and Staniforth, D., 1992, The tolerance to and pharmacokinetics of penciclovir (BRL 39123A), a novel antiherpes agent, administered by intravenous infusion to healthy subjects, Eur. J. Clin. Pharmacol. 43:513–516.

    CAS  PubMed  Google Scholar 

  • Fowles, S. E., Pratt, S. K., Laroche, J., and Prince, W. T., 1994, Lack of a pharmacokinetic interaction between oralfamciclovir and allopurinol in healthy volunteers, Eur. J. Clin. Pharmacol. 46:355–359.

    Article  CAS  PubMed  Google Scholar 

  • Geen, G. R., Harnden, M. R., and Parratt, M. J., 1991, Synthesis of 9-[2,2-bis(hydroxymethyl)cycloprop-1-yl]guanine as a potential antiviral agent, Bio Med. Chem. Lett. 1:347–348.

    CAS  Google Scholar 

  • Goldthorpe, S. E., Boyd, M. R., and Field, H. J., 1992, Effects of penciclovir and famciclovir in a murine model of encephalitis induced by intranasal inoculation of herpes simplex virus type 1, Antiviral Chem. Chemother. 3:37–47.

    CAS  Google Scholar 

  • Harnden, M. R., and Jarvest, R. L., 1985, An improved synthesis of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine, Tetrahedron Lett. 26:4265–4268.

    Article  CAS  Google Scholar 

  • Harnden, M. R., and Jarvest, R. L., 1988a, Analogues of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbutyl)guanine. Part 3. Modification of a 3′-hydroxymethyl group, J. Chem. Soc. Perkin Trans. 1 1988:2777–2784.

    Google Scholar 

  • Harnden, M. R., and Jarvest, R. L., 1988b, Synthesis of 9-(3-hydroxyalkylamino)guanines, novel antiviral acyclonucleosides, Tetrahedron Lett. 29:5995–5998.

    CAS  Google Scholar 

  • Harnden, M. R., and Jarvest, R. L., 1989, Analogues of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbutyl)guanine. Part 4. Substitution on the 2-amino group, J. Chem. Soc. Perkin Trans. 1 1989:2207–2213.

    Google Scholar 

  • Harnden, M. R., Jarvest, R. L., Bacon, T. H., and Boyd, M. R., 1987, Synthesis and antiviral activity of 9-[4-hydroxy-3-(hydroxymethyl)-but-l-y1]purines, J. Med. Chem. 30:1636–1642.

    Article  CAS  PubMed  Google Scholar 

  • Harnden, M, R., Parkin, A., and Wyatt, P. G., 1988a, Analogues of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbutyl)guanine. Part 1. Substitution on C-2′ of the acyclic N-9 substituent, J. Chem. Soc. Perkin Trans. 1 1988:2757–2765.

    Google Scholar 

  • Harnden, M. R., Parkin, A., and Wyatt, P. G., 1988b, Synthesis of 9-(3-hydroxypropoxy)guanine, a novel antiviral acyclonucleoside. Tetrahedron Lett. 29:701–704.

    CAS  Google Scholar 

  • Harnden, M. R., Jarvest, R. L., Boyd, M. R., Sutton, D., and Vere Hodge, R. A., 1989, Prodrugs of the selective antiherpesvirus agent 9-(4-hydroxy-3-(hydroxymethyl)-but-1-yl)guanine (BRL 39123) with improved gastrointestinal absorption properties, J. Med. Chem. 32:1738–1743.

    Article  PubMed  Google Scholar 

  • Harnden, M. R., Jarvest, R. L., Slawin, A. M. Z., and Williams, D. J., 1990a, Crystal and molecular structure of the antiviral acyclonucleoside 9-[4-hydroxy-3-(hydroxymethyl)butyl]guanine (BRL 39123, penciclovir) and its prodrug 9-[4-acetoxy-3-(acetoxymethyl)butyl]-2-aminopurine (BRL 42810, famciclovir), Nucleosides Nucleotides 9:499–513.

    CAS  Google Scholar 

  • Harnden, M. R., Wyatt, P. G., Boyd, M. R., and Sutton, D., 1990b, Synthesis and antiviral activity of 9-alkoxypurines. 1. 9-(3-hydroxypropoxy)-and 9-[3-hydroxy-2-hydroxymethyl)propoxy]-purines, J. Med. Chem. 33:187–196.

    Article  CAS  PubMed  Google Scholar 

  • Ilsley, D. D., Lee, S.-K., Miller, W. H., and Kuchta, R. D., 1995, Acyclic guanosine analogues inhibit DNA polymerases α, δ, and ε with very different properties and have unique mechanisms of action, Biochemistry 34:2504–2510.

    Article  CAS  PubMed  Google Scholar 

  • Jacobson, M. A., de Miranda, P., Cederberg, D. M., Burnett, T., Cobb, E., Brodie, H. R., and Mills, J., 1987, Human pharmacokinetics and tolerance of oral ganciclovir, Antimicrob. Agents Chemother. 31:1251–1254.

    CAS  PubMed  Google Scholar 

  • Jarvest, R. L., Barnes, R. D., Earnshaw, D. L., O’Toole, K. J., Sime, J. T., and Vere Hodge, R. A., 1990, Synthesis of isotopically chiral [13C] penciclovir (BRL 39123) and its use to determine the absolute configuration of penciclovir triphosphate formed in herpes virus infected cells, J. Chem. Soc. Chem. Commun. 1990:555–556.

    Google Scholar 

  • Karlson, A. H. J., Harmenberg, J. G., and Wahren, B. E., 1986, Influence of acyclovir and bucyclovir on nucleotide pools in cells infected with herpes simplex virus type 1, Antimicrob. Agents Chemother. 29:821–824.

    Google Scholar 

  • Korba, B. E., and Boyd, M. R., 1996, Penciclovir is a selective inhibitor of hepatitis B virus replication in cultured human hepatoblastoma cells, Antimicrob. Agents Chemother 40:1282–1284.

    CAS  PubMed  Google Scholar 

  • Krenitsky, T. A., Hall, W. W., de Miranda, P., Beauchamp, L. M., Schaeffer, H. J., and Whiteman, P. D., 1984, 6-Deoxyacyclovir: A xanthine oxidase-activated prodrug of acyclovir, Proc. Natl. Acad. Sci. USA 81:3209–3213.

    CAS  PubMed  Google Scholar 

  • Krüger, M., Tillmann, H. L., Trautwein, C., Bode, V., Oldhafer, K., Boker, K. H. W., Pichlmayr, R., and Manns, M. P., 1994, Treatment of hepatitis B virus reinfection after liver transplantation with famciclovir, in: 45th Meeting of the American Association for the Study of Liver Diseases, Chicago (Poster).

    Google Scholar 

  • Krüger, M., Tillmann, H. L., Trautwein, C., Bode, V, Oldhafer, K., Maschek, H., Boker, H., Broelsch, C. E., Pichlmayr, R., and Manns, M. P., 1996, Famciclovir treatment of hepatitis B virus recurrence after liver transplantation: A pilot study. Liver Transplant. Surg. 2:253–262.

    Google Scholar 

  • Larsson, A., Stenberg, A.-C., Ericson, U., Haglund, W.-A., Yisak, N.-G., Johansson, B., Öberg, B., and Datema, R., 1986, Mode of action, toxicity, pharmacokinetics and efficacy of some new antiherpesvirus guanosine analogs related to buciclovir, Antimicrob. Agents Chemother. 30:598–605.

    CAS  PubMed  Google Scholar 

  • Lin, E., Luscombe, C., Wang, Y. Y., Shaw, T., and Locarnini, S., 1996, The guanine nucleoside analogue penciclovir is active against chronic duck hepatitis B virus infection in vivo, Antimicrob. Agents Chemother. 2:413–4l8.

    Google Scholar 

  • Loveless, M., Harris, W., and Sacks, S., 1995, Treatment of first episode genital herpes with famciclovir, in: Abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, American Society for Microbiology.

    Google Scholar 

  • Lowe, D. M., Alderton, W. K., Ellis, M. R., Parmar, V., Miller, W. H., Roberts, A. B., Fyfe, J. A., Gaillard, R., Ertl, P., Snowden, W., and Littler, E., 1995, Mode of action of (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine against herpesvirus, Antimicrob. Agents Chemother. 39:1802–1808.

    CAS  PubMed  Google Scholar 

  • MacCoss, M., Tolman, R. L., Ashton, W. T., Wagner, A. F., Hannah, J., Field, A. K., Karkas, J. D., and Germershausen, J. I., 1986, Synthetic, biochemical and antiviral aspects of selected acyclonucleosides and their derivatives, Chem. Scri. 26:113–121.

    CAS  Google Scholar 

  • Mok, S. S., Shaw, T., and Locarnini, S., 1995, Preferential inhibition of hepatitis B virus (HBV) DNA polymerase by the (R)-enantiomer of penciclovir triphosphate, in: Abstracts of the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, American Society for Microbiology.

    Google Scholar 

  • Perry, C. M., and Wagstaff, A. J., 1995, Famciclovir, a review of its pharmacological properties and therapeutic efficacy in herpes virus infection, Drugs 50:396–415.

    CAS  PubMed  Google Scholar 

  • Pratt, S. K., Fowles, S. E., Pierce, D. M., and Prince, W. T., 1991, An investigation of the interaction between cimetidine and famciclovir in non-patient volunteers, Br. J. Clin. Pharmacol. 32:656P–657P.

    Google Scholar 

  • Pratt, S. K., Pue, M. A., Fairless, A J., Fowles, S. E., Laroche, J., Bygate, E., Glenny, H., Daniels, S., and Freedman, P. S., 1993, The pharmacokinetics of penciclovir following intravenous administration to healthy elderly subjects, in: Program and Abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, American Society of Microbiology.

    Google Scholar 

  • Pratt, S. K., Pue, M. A., Fairless, A. J., Fowles, S. E., Laroche, J., Kumar, R., and Prince, W. T., 1994a, Lack of an effect of gender on the pharmacokinetics of penciclovir, following single oral doses of famciclovir, Br. J. Clin. Pharmacol. 37:493P.

    Google Scholar 

  • Pratt, S. K., Standring-Cox, R., Writer, D., Brooks, S., Fowles, S. E., Fiala, S., Schubert, C., and Hust, R., 1994b, Penciclovir pharmacokinetics in fed and fasted subjects following oral famciclovir in relation to in-vitro antiviral activity, in: Book of Abstracts of the 6th International Congress for Infectious Diseases, Prague.

    Google Scholar 

  • Pue, M. A., and Benet, L. Z., 1993, Pharmacokinetics of famciclovir in man, Antiviral Chem. Chemother. 4(Suppl. l):47–55.

    CAS  Google Scholar 

  • Pue, M. A., Pratt, S. K., Fairless, A. J., Fowles, S., Laroche, J., Georgiou, P., and Prince, W., 1994, Linear pharmacokinetics of penciclovir following administration of single oral doses of famciclovir 125, 250, 500 and 750 mg to healthy volunteers, J. Antimicrob. Chemother. 33:119–127.

    CAS  PubMed  Google Scholar 

  • Raborn, G. W., and the Penciclovir Topical Collaborative Study Group, 1996, Penciclovir cream for recurrent herpes simplex labialis: An effective new treatment, in: Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, American Society for Microbiology.

    Google Scholar 

  • Reardon, J. E., and Spector, T., 1989, Herpes simplex virus type 1 DNA polymerase. Mechanism of inhibition by acyclovir triphosphate, J. Biol. Chem. 264:7405–7111.

    CAS  PubMed  Google Scholar 

  • Sacks, S. L., Bebault, G. M., Rennie, B. A., Wall, R. A., Vere Hodge, R. A., and Strauss, S. E., 1994, Virus-specified phosphorylation of penciclovir in a human schwannoma continuous cell line infected with varicella zoster virus, in: Abstracts of the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy, Orlando, American Society for Microbiology.

    Google Scholar 

  • Sacks, S. L., Aoki, F. Y., Diaz-Mitoma, F., Sellors, J., and Shafran, S. D., 1996, Patient initiated, twice daily oral famciclovir for early recurrent genital herpes: A Canadian multicenter trail, J. Am. Med. Assoc. 276:44–49.

    Article  CAS  Google Scholar 

  • Saltzman, R., Jurewicz, R., and Boon, R., 1994, The safety of famciclovir in patients with herpes zoster virus and genital herpes virus, Antimicrob. Agents Chemother. 38:2454–2457.

    CAS  PubMed  Google Scholar 

  • Shaw, T., Amor, P., Civitico, G., Boyd, M., and Locarnini, S., 1994, In vitro antiviral activity of penciclovir, a novel purine nucleoside, against duck hepatitis B virus, Antimicrob. Agents Chemother, 38:719–723.

    CAS  PubMed  Google Scholar 

  • Sime, J. T, Barnes, R. D., Elson, S. W., Jarvest, R. L., and O’Toole, K. J., 1992, Chemoenzymatic approach to the synthesis of the antiviral agents penciclovir and famciclovir in isotopically chiral [13C] labelled form, J. Chem. Soc. Perkin Tram. I 1992:1653–1658.

    Google Scholar 

  • Spruance, S. L., 1996, Penciclovir cream: A new and effective treatment for recurrent herpes simplex labialis (abstract), in: Congress of Clinical Dermatology 2000, Vancouver, Canada.

    Google Scholar 

  • Sutton, D., and Boyd, M. R., 1993, Comparative activity of penciclovir and acyclovir in mice infected intraperitoneally with herpes simplex virus type 1 SC16, Antimicrob. Agents Chemother. 37:642–645.

    CAS  PubMed  Google Scholar 

  • Sutton, D., and Kern, E. R., 1993, Activity of famciclovir and penciclovir in HSV-infected animals: A review, Antiviral Chem. Chemother. 4(Suppl. l):37–46.

    CAS  Google Scholar 

  • Talarico, C. L., Phelps, W. C., and Biron, K. K., 1993, Analysis of the thymidine kinase genes from acyclovir-resistant mutants of varicella zoster virus isolated from patients with AIDS, J. Virol. 67:1024–1033.

    CAS  PubMed  Google Scholar 

  • Thackray, A. M., and Field, H. J., 1996a, Differential effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus in a murine infection model including reactivation from latency, J. Infect. Dis. 173:291–299.

    CAS  PubMed  Google Scholar 

  • Thackray, A. M., and Field, H. J., 1996b, Comparison of the effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus type 2 in a murine infection model, Antimicrob. Agents Chemother. 40:846–851.

    CAS  PubMed  Google Scholar 

  • Tippie, M. A., Martin, J. C., Smee, D. F., Matthews, T. R., and Verheyden, J.P.H., 1984, Antiherpes simplex virus activity of 9-[4-hydroxy-3-(hydroxymethyl)-1-butyl]guanine, Nucleosides Nucleotides 3:525–535.

    CAS  Google Scholar 

  • Tsiquaye, K. N., Slomka, M. J., and Maung, M., 1994, Oral famciclovir against duck hepatitis B virus replication in hepatic and nonhepatic tissues of ducklings infected in ovo, J. Med. Virol. 42:306–310.

    CAS  PubMed  Google Scholar 

  • Tsiquaye, K. N., Sutton, D., Maung, M., and Boyd, M. R., 1996, Antiviral activities and pharmacokinetics of penciclovir and famciclovir in Peking ducks chronically infected with duck hepatitis virus, Antiviral Chem. Chemother. 7:153–159.

    CAS  Google Scholar 

  • Tyring, S., Barbarash, R. A., Nahlik, J., et al., 1995, Famciclovir for the treatment of acute herpes zoster: Effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial, Ann. Intern. Med. 123:89–96.

    CAS  PubMed  Google Scholar 

  • Vere Hodge, R. A., 1993, Famciclovir and penciclovir. The mode of action of famciclovir including its conversion to penciclovir, Antiviral Chem. Chemother. 4:67–84.

    CAS  Google Scholar 

  • Vere Hodge, R. A., and Cheng, Y.-C., 1993, Mode of action of penciclovir, Antiviral Chem. Chemother. 4(Suppl. 1): 13–24.

    Google Scholar 

  • Vere Hodge, R. A., and Perkins, R. M., 1989, Mode of action of 9-(4-hydroxy-3-hydroxymethylbut-l-yl)guanine (BRL 39123) against herpessimplex virus in MRC-5 cells, Antimicrob. Agents Chemother. 33:223–229.

    Google Scholar 

  • Vere Hodge, R. A., Sutton, D., Boyd, M. R., Harnden, M. R., and Jarvest, R. L., 1989, Selection of an oral prodrug (BRL 42810; famciclovir) for the antiherpesvirus agent BRL 39123 [9-(4-hydroxy-3-(hydroxymethyl)but-1-yl)guanine; penciclovir], Antimicrob. Agents Chemother. 33:1765–1773.

    CAS  PubMed  Google Scholar 

  • Vere Hodge, R. A., Darlison, S. J., Earnshaw, D. L., and Readshaw, S. A., 1993a, Use of isotopically chiral [4′-13C]penciclovir and 13C NMR to determine the specificity and absolute configuration of penciclovir phosphate esters formed in HSV-1 and HSV-2 infected cells and by HSV-1 encoded thymidine kinase, Chirality 5:583–588.

    CAS  PubMed  Google Scholar 

  • Vere Hodge, R. A., Darlison, S. J., Earnshaw, D. L., and Readshaw, S. A., 1993b, Use of isotopically chiral [4′-3]famciclovir and 13C NMR to identify the chiral monoacetylated intermediates in the conversion of famciclovir to penciclovir by human intestinal wall extract, Chirality 5:577–582.

    CAS  PubMed  Google Scholar 

  • Weller, S., Blum, M. R., Doucette, M., Burnette, T., Cederberg, D. M., de Miranda, P., and Smiley, M. L., 1993, Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single-and multiple-dose administration to normal volunteers, Clin. Pharmacol. Ther. 54:595–605.

    CAS  PubMed  Google Scholar 

  • Yamaoka, Y., Roberts, R. D., and Stella, V. J., 1983, Low-melting phenytoin prodrugs as alternative oral delivery modes for phenytoin: A model for other high-melting sparingly water-soluble drugs, J. Pharm. Sci. 72:400–405.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Smith Kline Beecham Pharmaceuticals, Harlow, Essex, CM 19 5AW, England

    Richard L. Jarvest, David Sutton & R. Anthony Vere Hodge

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  1. Richard L. Jarvest
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  2. David Sutton
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  3. R. Anthony Vere Hodge
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Editors and Affiliations

  1. The University of Kansas, Lawrence, Kansas

    Ronald T. Borchardt

  2. Merck Research Laboratories, West Point, Pennsylvania

    Roger M. Freidinger

  3. ARIAD Pharmaceuticals, Inc., Cambridge, Massachusetts

    Tomi K. Sawyer

  4. Smith Kline Beecham, Collegeville, Pennsylvania

    Philip L. Smith

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© 2002 Kluwer Academic Publishers

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Jarvest, R.L., Sutton, D., Vere Hodge, R.A. (2002). Famciclovir. In: Borchardt, R.T., Freidinger, R.M., Sawyer, T.K., Smith, P.L. (eds) Integration of Pharmaceutical Discovery and Development. Pharmaceutical Biotechnology, vol 11. Springer, Boston, MA. https://doi.org/10.1007/0-306-47384-4_14

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  • DOI: https://doi.org/10.1007/0-306-47384-4_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-306-45743-2

  • Online ISBN: 978-0-306-47384-5

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