Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients

Hugh Wiltshire, Carlos V. Paya, Mark D. Pescovitz, Atul Humar, Edward Dominguez, Kenneth Washburn, Emily Blumberg, Barbara Alexander, Richard Freeman, Nigel Heaton, Klaas P. Zuideveld, Rene Bouw

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Background. A randomized, double-blind study was conducted to evaluate the pharmacokinetics of ganciclovir following oral administration of ganciclovir or valganciclovir for prophylaxis of cytomegalovirus (CMV) disease in solid organ transplant recipients (n = 240/372). Methods. The correlations between individual exposure to ganciclovir during prophylaxis, with CMV viremia incidence during and after treatment, CMV disease up to 12 months posttransplant, and hematological toxicity were assessed. Results. Mean daily areas under the curve (AUCs) of ganciclovir from valganciclovir and oral ganciclovir were 46.3 ± 15.2 and 28.0 ± 10.9 μg·h/ml (mean ± SD), respectively. Viremia was suppressed during prophylaxis when exposure to ganciclovir was 40-50 μg·h/ml, AUCs typical of those achieved in valganciclovir-treated patients. The development of viremia 1 month after ending prophylaxis was also reduced with higher ganciclovir AUC (median predicted incidence, 20% and 10% at AUCs of 33 and 50 μg h/ml, respectively). The development of CMV disease within 1 year of transplant was 17.6% and independent of prophylactic exposure to ganciclovir. There was only a weak tendency to increased neutropenia and leukopenia with higher ganciclovir exposure. Conclusions. The greater systemic exposure to ganciclovir delivered by valganciclovir was associated with delayed development of viremia. There was only a weak association between AUC and hematological toxicity.

Original languageEnglish (US)
Pages (from-to)1477-1483
Number of pages7
JournalTransplantation
Volume79
Issue number11
DOIs
StatePublished - Jun 15 2005

Keywords

  • Cytomegalovirus
  • Ganciclovir
  • Pharmacodynamics
  • Solid organ transplant
  • Valganciclovir

ASJC Scopus subject areas

  • Transplantation

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