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

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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

Fingerprint

Ganciclovir
Transplants
Viremia
Area Under Curve
Cytomegalovirus
valganciclovir
Transplant Recipients
Incidence
Leukopenia
Neutropenia
Double-Blind Method
Oral Administration
Pharmacokinetics

Keywords

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

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Wiltshire, H., Paya, C. V., Pescovitz, M. D., Humar, A., Dominguez, E., Washburn, K., ... Bouw, R. (2005). Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients. Transplantation, 79(11), 1477-1483. https://doi.org/10.1097/01.TP.0000164512.99703.AD

Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients. / Wiltshire, Hugh; Paya, Carlos V.; Pescovitz, Mark D.; Humar, Atul; Dominguez, Edward; Washburn, Kenneth; Blumberg, Emily; Alexander, Barbara; Freeman, Richard; Heaton, Nigel; Zuideveld, Klaas P.; Bouw, Rene.

In: Transplantation, Vol. 79, No. 11, 15.06.2005, p. 1477-1483.

Research output: Contribution to journalArticle

Wiltshire, H, Paya, CV, Pescovitz, MD, Humar, A, Dominguez, E, Washburn, K, Blumberg, E, Alexander, B, Freeman, R, Heaton, N, Zuideveld, KP & Bouw, R 2005, 'Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients', Transplantation, vol. 79, no. 11, pp. 1477-1483. https://doi.org/10.1097/01.TP.0000164512.99703.AD
Wiltshire H, Paya CV, Pescovitz MD, Humar A, Dominguez E, Washburn K et al. Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients. Transplantation. 2005 Jun 15;79(11):1477-1483. https://doi.org/10.1097/01.TP.0000164512.99703.AD
Wiltshire, Hugh ; Paya, Carlos V. ; Pescovitz, Mark D. ; Humar, Atul ; Dominguez, Edward ; Washburn, Kenneth ; Blumberg, Emily ; Alexander, Barbara ; Freeman, Richard ; Heaton, Nigel ; Zuideveld, Klaas P. ; Bouw, Rene. / Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant recipients. In: Transplantation. 2005 ; Vol. 79, No. 11. pp. 1477-1483.
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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.",
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AU - Wiltshire, Hugh

AU - Paya, Carlos V.

AU - Pescovitz, Mark D.

AU - Humar, Atul

AU - Dominguez, Edward

AU - Washburn, Kenneth

AU - Blumberg, Emily

AU - Alexander, Barbara

AU - Freeman, Richard

AU - Heaton, Nigel

AU - Zuideveld, Klaas P.

AU - Bouw, Rene

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N2 - 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.

AB - 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.

KW - Cytomegalovirus

KW - Ganciclovir

KW - Pharmacodynamics

KW - Solid organ transplant

KW - Valganciclovir

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