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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.


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