FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 335:721-729 September 5, 1996 Number 10 Next

	Since this article has no abstract, we have provided an extract of the first 100 words of the full text and any section headings.

	Full Text PDF Purchase this article Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Ganciclovir is a nucleoside analogue of guanosine, a homologue of acyclovir, and the first antiviral drug to be effective in the treatment of cytomegalovirus (CMV) disease in humans.^1,2,3,4 It inhibits not only all the herpesviruses but also the transformation of normal cord-blood lymphocytes by Epstein–Barr virus.^5,6,7 In this review, I outline ganciclovir's mechanisms of action and resistance and discuss the clinical effectiveness of intravenous and oral ganciclovir.

Mechanism of Action

The structures of ganciclovir and of its analogue acyclovir are shown in Figure 1. In vivo, ganciclovir is converted to ganciclovir triphosphate, which inhibits viral DNA polymerases, including those of herpes simplex . . . [Full Text of this Article]

Intracellular Phosphorylation of Ganciclovir

Cytotoxicity

Mechanisms of Resistance

Clinical Importance of Resistance to Ganciclovir

Antiviral Spectrum

Pharmacokinetics of Intravenous and Oral Ganciclovir

Clinical Uses

Treatment of CMV Infections

            CMV Retinitis

            Infections of the Gastrointestinal Tract

            Pneumonia

            Infection of the Nervous System

Prevention of CMV Disease

Toxicity

Alternative Therapies

Conclusions

Source Information

From the Division of Infectious Disease, Beth Israel Hospital, 330 Brookline Ave., Boston, MA 02215, where reprint requests should be addressed to Dr. Crumpacker.

References

This article has been cited by other articles:

• Caldes, A., Colom, H., Armendariz, Y., Garrido, M. J., Troconiz, I. F., Gil-Vernet, S., Lloberas, N., Pou, L., Peraire, C., Grinyo, J. M. (2009). Population Pharmacokinetics of Ganciclovir after Intravenous Ganciclovir and Oral Valganciclovir Administration in Solid Organ Transplant Patients Infected with Cytomegalovirus. Antimicrob. Agents Chemother. 53: 4816-4824 [Abstract] [Full Text]  
• Trofe, J., Pote, L., Wade, E., Blumberg, E., Bloom, R. D (2008). Maribavir: A Novel Antiviral Agent with Activity Against Cytomegalovirus. The Annals of Pharmacotherapy 42: 1447-1457 [Abstract] [Full Text]  
• Tan, B. H. (2006). CMV prophylaxis--to do or not to do, that is the question. Nephrol Dial Transplant 21: 1757-1761 [Full Text]  
• Naesens, L., Lenaerts, L., Andrei, G., Snoeck, R., Van Beers, D., Holy, A., Balzarini, J., De Clercq, E. (2005). Antiadenovirus Activities of Several Classes of Nucleoside and Nucleotide Analogues. Antimicrob. Agents Chemother. 49: 1010-1016 [Abstract] [Full Text]  
• Crumpacker, C. S. (2004). Use of Antiviral Drugs to Prevent Herpesvirus Transmission. NEJM 350: 67-68 [Full Text]  
• Sergerie, Y., Boivin, G. (2003). Evaluation of Susceptibility of Human Herpesvirus 8 to Antiviral Drugs by Quantitative Real-Time PCR. J. Clin. Microbiol. 41: 3897-3900 [Abstract] [Full Text]  
• Williams, S. L., Hartline, C. B., Kushner, N. L., Harden, E. A., Bidanset, D. J., Drach, J. C., Townsend, L. B., Underwood, M. R., Biron, K. K., Kern, E. R. (2003). In Vitro Activities of Benzimidazole D- and L-Ribonucleosides against Herpesviruses. Antimicrob. Agents Chemother. 47: 2186-2192 [Abstract] [Full Text]  
• Wolf, D. L., Rodriguez, C. A., Mucci, M., Ingrosso, A., Duncan, B. A., Nickens, D. J. (2003). Pharmacokinetics and Renal Effects of Cidofovir with a Reduced Dose of Probenecid in HIV-Infected Patients with Cytomegalovirus Retinitis. J Clin Pharmacol 43: 43-51 [Abstract] [Full Text]  
• Adachi, M., Sampath, J., Lan, L.-b., Sun, D., Hargrove, P., Flatley, R., Tatum, A., Edwards, M. Z., Wezeman, M., Matherly, L., Drake, R., Schuetz, J. (2002). Expression of MRP4 Confers Resistance to Ganciclovir and Compromises Bystander Cell Killing. J. Biol. Chem. 277: 38998-39004 [Abstract] [Full Text]  
• Biron, K. K., Harvey, R. J., Chamberlain, S. C., Good, S. S., Smith, A. A. III, Davis, M. G., Talarico, C. L., Miller, W. H., Ferris, R., Dornsife, R. E., Stanat, S. C., Drach, J. C., Townsend, L. B., Koszalka, G. W. (2002). Potent and Selective Inhibition of Human Cytomegalovirus Replication by 1263W94, a Benzimidazole L-Riboside with a Unique Mode of Action. Antimicrob. Agents Chemother. 46: 2365-2372 [Abstract] [Full Text]  
• Zaidi, S. A., Cervia, J. S. (2002). Diagnosis and Management of Infectious Esophagitis Associated with Human Immunodeficiency Virus Infection. J Int Assoc Physicians AIDS Care (Chic Ill) 1: 53-62 [Abstract]  
• Reusser, P., Einsele, H., Lee, J., Volin, L., Rovira, M., Engelhard, D., Finke, J., Cordonnier, C., Link, H., Ljungman, P. (2002). Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood 99: 1159-1164 [Abstract] [Full Text]  
• McSharry, J. J., McDonough, A., Olson, B., Talarico, C., Davis, M., Biron, K. K. (2001). Inhibition of Ganciclovir-Susceptible and -Resistant Human Cytomegalovirus Clinical Isolates by the Benzimidazole L-Riboside 1263W94. CVI 8: 1279-1281 [Abstract] [Full Text]  
• Manichanh, C., Olivier-Aubron, C., Lagarde, J.-P., Aubin, J.-T., Bossi, P., Gautheret-Dejean, A., Huraux, J.-M., Agut, H. (2001). Selection of the same mutation in the U69 protein kinase gene of human herpesvirus-6 after prolonged exposure to ganciclovir in vitro and in vivo. J. Gen. Virol. 82: 2767-2776 [Abstract] [Full Text]  
• Lurain, N. S., Weinberg, A., Crumpacker, C. S., Chou, S. (2001). Sequencing of Cytomegalovirus UL97 Gene for Genotypic Antiviral Resistance Testing. Antimicrob. Agents Chemother. 45: 2775-2780 [Abstract] [Full Text]  
• McSharry, J. J., McDonough, A., Olson, B., Hallenberger, S., Reefschlaeger, J., Bender, W., Drusano, G. L. (2001). Susceptibilities of Human Cytomegalovirus Clinical Isolates to BAY38-4766, BAY43-9695, and Ganciclovir. Antimicrob. Agents Chemother. 45: 2925-2927 [Abstract] [Full Text]  
• Moore, S. M., Cannon, J. S., Tanhehco, Y. C., Hamzeh, F. M., Ambinder, R. F. (2001). Induction of Epstein-Barr Virus Kinases To Sensitize Tumor Cells to Nucleoside Analogues. Antimicrob. Agents Chemother. 45: 2082-2091 [Abstract] [Full Text]  
• BRENNAN, D. C. (2001). Cytomegalovirus in Renal Transplantation. J. Am. Soc. Nephrol. 12: 848-855 [Full Text]  
• Wolf, D. G., Courcelle, C. T., Prichard, M. N., Mocarski, E. S. (2001). Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. Proc. Natl. Acad. Sci. USA 98: 1895-1900 [Abstract] [Full Text]  
• Wolf, D. G., Yaniv, I., Ashkenazi, S., Honigman, A. (2001). Emergence of Multiple Human Cytomegalovirus Ganciclovir-Resistant Mutants with Deletions and Substitutions within the UL97 Gene in a Patient with Severe Combined Immunodeficiency. Antimicrob. Agents Chemother. 45: 593-595 [Abstract] [Full Text]  
• Meeus, G., Messiaen, T., Verhoef, G., Vanrenterghem, Y. (2000). New-onset anaemia following kidney transplantation. Nephrol Dial Transplant 15: 2059-2061 [Full Text]  
• Sia, I. G., Patel, R. (2000). New Strategies for Prevention and Therapy of Cytomegalovirus Infection and Disease in Solid-Organ Transplant Recipients. Clin. Microbiol. Rev. 13: 83-121 [Abstract] [Full Text]  
• Gustafson, E. A., Schinazi, R. F., Fingeroth, J. D. (2000). Human Herpesvirus 8 Open Reading Frame 21 Is a Thymidine and Thymidylate Kinase of Narrow Substrate Specificity That Efficiently Phosphorylates Zidovudine but Not Ganciclovir. J. Virol. 74: 684-692 [Abstract] [Full Text]  
• Gerbase, M. W., Dubois, D., Rothmeier, C., Spiliopoulos, A., Wunderli, W., Nicod, L. P. (1999). Costs and Outcomes of Prolonged Cytomegalovirus Prophylaxis to Cover the Enhanced Immunosuppression Phase Following Lung Transplantation. Chest 116: 1265-1272 [Abstract] [Full Text]  
• Emery, V. C., Cope, A. V., Bowen, E. F., Gor, D., Griffiths, P. D. (1999). The Dynamics of Human Cytomegalovirus Replication in Vivo. JEM 190: 177-182 [Abstract] [Full Text]  
• Cohen, J. I., Brunell, P. A., Straus, S. E., Krause, P. R. (1999). Recent Advances in Varicella-Zoster Virus Infection. ANN INTERN MED 130: 922-932 [Abstract] [Full Text]  
• Balfour, H. H. (1999). Antiviral Drugs. NEJM 340: 1255-1268 [Full Text]  
• Erice, A. (1999). Resistance of Human Cytomegalovirus to Antiviral Drugs. Clin. Microbiol. Rev. 12: 286-297 [Abstract] [Full Text]  
• Fischler, B., Rodensjö, P., Nemeth, A., Forsgren, M., Lewensohn-Fuchs, I. (1999). Cytomegalovirus DNA detection on Guthrie cards in patients with neonatal cholestasis. Arch. Dis. Child. Fetal Neonatal Ed. 80: 130F-134 [Abstract] [Full Text]  
• McSharry, J. J., Lurain, N. S., Drusano, G. L., Landay, A. L., Notka, M., O'Gorman, M. R. G., Weinberg, A., Shapiro, H. M., Reichelderfer, P. S., Crumpacker, C. S. (1998). Rapid Ganciclovir Susceptibility Assay Using Flow Cytometry for Human Cytomegalovirus Clinical Isolates. Antimicrob. Agents Chemother. 42: 2326-2331 [Abstract] [Full Text]  
• McSharry, J. M., Lurain, N. S., Drusano, G. L., Landay, A., Manischewitz, J., Nokta, M., O'Gorman, M., Shapiro, H. M., Weinberg, A., Reichelderfer, P., Crumpacker, C. (1998). Flow Cytometric Determination of Ganciclovir Susceptibilities of Human Cytomegalovirus Clinical Isolates. J. Clin. Microbiol. 36: 958-964 [Abstract] [Full Text]  
• Jacobson, M. A. (1997). Treatment of Cytomegalovirus Retinitis in Patients with the Acquired Immunodeficiency Syndrome. NEJM 337: 105-114 [Full Text]  
• Lemstrom, K., Sihvola, R., Bruggeman, C., Hayry, P., Koskinen, P. (1997). Cytomegalovirus Infection–Enhanced Cardiac Allograft Vasculopathy Is Abolished by DHPG Prophylaxis in the Rat. Circulation 95: 2614-2616 [Abstract] [Full Text]  
• Jackson, J. L., Gibbons, R., Meyer, G., Inouye, L. (1997). The Effect of Treating Herpes Zoster With Oral Acyclovir in Preventing Postherpetic Neuralgia: A Meta-analysis. Arch Intern Med 157: 909-912 [Abstract]  
• Emery, V. C., Griffiths, P. D. (2000). Prediction of cytomegalovirus load and resistance patterns after antiviral chemotherapy. Proc. Natl. Acad. Sci. USA 97: 8039-8044 [Abstract] [Full Text]