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Clin Pharmacokinet 2005; 44 (5): 495-507 ORIGINAL RESEARCH ARTICLE 0312-5963/05/0005-0495/$34.95/0 2005 Adis Data Information BV. All rights reserved. Pharmacokinetic Profile of Ganciclovir After its Oral Administration and From its Prodrug, Valganciclovir, in Solid Organ Transplant Recipients Hugh Wiltshire, 1 Sarapee Hirankarn, 2 Colm Farrell, 2 Carlos Paya, 3 Mark D. Pescovitz, 4 Atul Humar, 5 Edward Dominguez, 6 Kenneth Washburn, 7 Emily Blumberg, 8 Barbara Alexander, 9 Richard Freeman, 10 Nigel Heaton 11 and The Valganciclovir Solid Organ Transplant Study Group 1 Roche Products Ltd, Welwyn Garden City, UK 2 GloboMax – a division of ICON plc., Marlow, UK 3 Mayo Clinic, Rochester, New York, USA 4 Departments of Surgery/Microbiology/Immunology, Indiana University, Indianapolis, Indiana, USA 5 Toronto General Hospital, Toronto, Ontario, Canada 6 University of Nebraska Medical Center, Omaha, Nebraska, USA 7 University of Texas Health Science Center, San Antonio, Texas, USA 8 Hospital of the University of Pennsylvania, Philadelphia, Pennsylvannia, USA 9 Duke University Medical Center, Durham, North Carolina, USA 10 New England Medical Center, Boston, Massachusetts, USA 11 King’s College, London, UK Background: Valganciclovir (Valcyte ) has recently been approved for the Abstract prevention of cytomegalovirus (CMV) disease in high-risk (CMV donor posi- tive [D+]/recipient negative [R–]) solid organ transplant (SOT) recipients. Large- -scale studies describing the pharmacokinetics of valganciclovir in SOT recipients are lacking. A recent randomised, double-blind study of valganciclovir in 364 D+/R– (intent-to-treat population) SOT recipients provided valuable data on which a population pharmacokinetic analysis was performed. Methods: The pharmacokinetics of ganciclovir from oral ganciclovir (Cymevene , 1000mg three times daily) and from valganciclovir (900mg once daily) were described with plasma levels from 240 patients (1181 datapoints describing 449 pharmacokinetic profiles) using nonlinear mixed-effects model- ling (NONMEM) software. A two-compartment pharmacokinetic model with separate absorption/metabolism and absorption parameters for valganciclovir and ganciclovir, respectively, was developed. Results: Exposure to ganciclovir from valganciclovir averaged 1.65-fold greater than that from oral ganciclovir (95% CI 1.58, 1.81); respective daily area
