This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pescovitz, M. D.
Right arrow Articles by Brown, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pescovitz, M. D.
Right arrow Articles by Brown, F.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, October 2000, p. 2811-2815, Vol. 44, No. 10
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Valganciclovir Results in Improved Oral Absorption of Ganciclovir in Liver Transplant Recipients

Mark D. Pescovitz,1,* John Rabkin,2 Robert M. Merion,3 Carlos V. Paya,4 John Pirsch,5 R. B. Freeman,6 John O'Grady,7 Charles Robinson,8 Zung To,8 Kristina Wren,8 Ludger Banken,9 William Buhles,8 and Frances Brown10

Transplantation Section, Department of Surgery, and Department of Microbiology/Immunology, Indiana University, Indianapolis, Indiana 426021; Liver/Pancreas Transplant Section, Oregon Health Sciences University, Portland, Oregon 972012; University of Michigan Medical Center, Ann Arbor, Michigan 481093; Divisions of Infectious Diseases and Transplantation, Liver Transplant Unit, Mayo Clinic, Rochester, Minnesota 559054; Department of Surgery, University Hospital, University of Wisconsin, Madison, Wisconsin 537925; Division of Transplant Surgery, New England Medical Center, Boston, Massachusetts 021116; Institute of Liver Studies, King's College School of Medicine and Dentistry, London, SE5 9JP,7 and Roche Products Ltd., Welwyn Garden City, Herts, AL7 3AY,10 United Kingdom; Roche Global Development, Palo Alto, California 943048; and F. Hoffman-La Roche AG, 4070 Basel, Switzerland9

Received 27 January 2000/Returned for modification 13 June 2000/Accepted 18 July 2000

The pharmacokinetics of an orally administered valine ester of ganciclovir (GCV), valganciclovir (VGC), were studied. These were compared to the pharmacokinetics of oral and intravenous GCV. Twenty-eight liver transplant recipients received, in an open-label random order with a 3- to 7-day washout, each of the following: 1 g of oral GCV three times a day; 450 mg of VGC per os (p.o.) once a day (q.d.); 900 mg of VGC p.o. q.d.; and 5 mg of intravenous (i.v.) GCV per kg of body weight q.d., given over 1 h. GCV and VGC concentrations were measured in blood over 24 h. One-sided equivalence testing was performed to test for noninferiority of 450 mg of VGC relative to oral GCV (two-sided 90% confidence interval [CI] > 80%) and nonsuperiority of 900 mg of VGC relative to i.v. GCV (two-sided 90% CI < 125%). The exposure of 450 mg of VGC (20.56 µg · h/ml) was found to be noninferior to that of oral GCV (20.15 µg · h/ml; 90% CI for relative bioavailability of 95 to 109%), and the exposure of 900 mg of VGC (42.69 µg · h/ml) was found to be nonsuperior to that of i.v. GCV (47.61 µg · h/ml; 90% CI = 83 to 97%). Oral VGC delivers systemic GCV exposure equivalent to that of standard oral GCV (at 450 mg) or i.v. GCV (at 900 mg of VGC). VGC has promise for effective CMV prophylaxis or treatment with once-daily oral dosing in transplant recipients.

* Corresponding author. Mailing address: Indiana University, Department of Surgery, UH4258, 550 N. University Blvd., Indianapolis, IN 46202-5253. Phone: (317) 274-4370. Fax: (317) 278-3268. E-mail: mpescov{at}iupui.edu.

Antimicrobial Agents and Chemotherapy, October 2000, p. 2811-2815, Vol. 44, No. 10
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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]  
  • Luan, F. L., Stuckey, L. J., Park, J. M., Kaul, D., Cibrik, D., Ojo, A. (2009). Six-Month Prophylaxis Is Cost Effective in Transplant Patients at High Risk for Cytomegalovirus Infection. J. Am. Soc. Nephrol. 20: 2449-2458 [Abstract] [Full Text]  
  • Tchesnokov, E. P., Obikhod, A., Schinazi, R. F., Gotte, M. (2009). Engineering of a Chimeric RB69 DNA Polymerase Sensitive to Drugs Targeting the Cytomegalovirus Enzyme. J. Biol. Chem. 284: 26439-26446 [Abstract] [Full Text]  
  • Perrottet, N., Csajka, C., Pascual, M., Manuel, O., Lamoth, F., Meylan, P., Aubert, J. D., Venetz, J. P., Soccal, P., Decosterd, L. A., Biollaz, J., Buclin, T. (2009). Population Pharmacokinetics of Ganciclovir in Solid-Organ Transplant Recipients Receiving Oral Valganciclovir. Antimicrob. Agents Chemother. 53: 3017-3023 [Abstract] [Full Text]  
  • Perrottet, N., Robatel, C., Meylan, P., Pascual, M., Venetz, J. P., Aubert, J. D., Berger, M. M., Decosterd, L. A., Buclin, T. (2008). Disposition of valganciclovir during continuous renal replacement therapy in two lung transplant recipients. J Antimicrob Chemother 61: 1332-1335 [Abstract] [Full Text]  
  • Lai, L., Xu, Z., Zhou, J., Lee, K.-D., Amidon, G. L. (2008). Molecular Basis of Prodrug Activation by Human Valacyclovirase, an {alpha}-Amino Acid Ester Hydrolase. J. Biol. Chem. 283: 9318-9327 [Abstract] [Full Text]  
  • McGuigan, C., Pathirana, R. N., Migliore, M., Adak, R., Luoni, G., Jones, A. T., Diez-Torrubia, A., Camarasa, M.-J., Velazquez, S., Henson, G., Verbeken, E., Sienaert, R., Naesens, L., Snoeck, R., Andrei, G., Balzarini, J. (2007). Preclinical development of bicyclic nucleoside analogues as potent and selective inhibitors of varicella zoster virus. J Antimicrob Chemother 60: 1316-1330 [Abstract] [Full Text]  
  • Cochrane, A. B. (2006). Antiviral dosing and efficacy for prophylaxis of cytomegalovirus disease in solid organ transplant recipients.. Am J Health Syst Pharm 63: S17-S21 [Abstract] [Full Text]  
  • Einsele, H., Reusser, P., Bornhauser, M., Kalhs, P., Ehninger, G., Hebart, H., Chalandon, Y., Kroger, N., Hertenstein, B., Rohde, F., for the EBMT Working Group on Infectious Disease, (2006). Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation. Blood 107: 3002-3008 [Abstract] [Full Text]  
  • Peyriere, H., Jeziorsky, E., Jalabert, A., Cociglio, M., Benketira, A., Blayac, J.-P., Hansel, S., Margueritte, G., Hillaire-Buys, D. (2006). Neurotoxicity Related to Valganciclovir in a Child with Impaired Renal Function: Usefulness of Therapeutic Drug Monitoring. The Annals of Pharmacotherapy 40: 143-146 [Abstract] [Full Text]  
  • Baillie, G. M. (2005). Pharmacokinetics of antiviral agents for the treatment of cytomegalovirus infection. Am J Health Syst Pharm 62: S14-S17 [Abstract] [Full Text]  
  • Gilbert, C., Boivin, G. (2005). Human Cytomegalovirus Resistance to Antiviral Drugs. Antimicrob. Agents Chemother. 49: 873-883 [Full Text]  
  • Fortun Abete, J., Martin-Davila, P., Moreno, S., Quijano, Y., de Vicente, E., Pou, L. (2004). Pharmacokinetics of Oral Valganciclovir and Intravenous Ganciclovir Administered to Prevent Cytomegalovirus Disease in an Adult Patient Receiving Small-Intestine Transplantation. Antimicrob. Agents Chemother. 48: 2782-2783 [Full Text]  
  • Kim, I., Chu, X.-y., Kim, S., Provoda, C. J., Lee, K.-D., Amidon, G. L. (2003). Identification of a Human Valacyclovirase: BIPHENYL HYDROLASE-LIKE PROTEIN AS VALACYCLOVIR HYDROLASE. J. Biol. Chem. 278: 25348-25356 [Abstract] [Full Text]  
  • Hicks, L. C. (2002). Home Health Care for the Kidney and Kidney-Pancreas Transplant Recipient. Home Health Care Management Practice 14: 289-294 [Abstract]  
  • Martin, D. F., Sierra-Madero, J., Walmsley, S., Wolitz, R. A., Macey, K., Georgiou, P., Robinson, C. A., Stempien, M. J., the Valganciclovir Study Group, (2002). A Controlled Trial of Valganciclovir as Induction Therapy for Cytomegalovirus Retinitis. NEJM 346: 1119-1126 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»