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Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients.

Publication ,  Journal Article
Wiltshire, H; Hirankarn, S; Farrell, C; Paya, C; Pescovitz, MD; Humar, A; Dominguez, E; Washburn, K; Blumberg, E; Alexander, B; Freeman, R ...
Published in: Clin Pharmacokinet
2005

BACKGROUND: Valganciclovir (Valcyte) has recently been approved for the prevention of cytomegalovirus (CMV) disease in high-risk (CMV donor positive [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, 1000 mg three times daily) and from valganciclovir (900 mg once daily) were described with plasma levels from 240 patients (1181 datapoints describing 449 pharmacokinetic profiles) using nonlinear mixed-effects modelling (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 under the plasma concentration-time curve values were 46.3 +/- 15.2 microg . h/mL and 28.0 +/- 10.9 microg . h/mL. The relative systemic exposure of ganciclovir was approximately 8-fold higher from valganciclovir than oral ganciclovir. Exposure to ganciclovir from valganciclovir was similar among liver, heart and kidney transplant recipients (46.0 +/- 16.1, 40.2 +/- 11.8 and 48.2 +/- 14.6 microg . h/ mL, respectively). Adherence to the prescribed dosing regimens, which were reduced for renal impairment, gave consistent exposure to ganciclovir. CONCLUSION: Oral valganciclovir produces exposures of ganciclovir exceeding those attained with oral ganciclovir, but in line with those reported after standard intravenous administration of ganciclovir. This indicates that oral valganciclovir is suitable in circumstances requiring prophylactic use of ganciclovir and allows for more convenient management of patients at risk of CMV disease.

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Published In

Clin Pharmacokinet

DOI

ISSN

0312-5963

Publication Date

2005

Volume

44

Issue

5

Start / End Page

495 / 507

Location

Switzerland

Related Subject Headings

  • Valganciclovir
  • Prodrugs
  • Pharmacology & Pharmacy
  • Organ Transplantation
  • Models, Biological
  • Middle Aged
  • Male
  • Humans
  • Ganciclovir
  • Female
 

Citation

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Wiltshire, H., Hirankarn, S., Farrell, C., Paya, C., Pescovitz, M. D., Humar, A., … Valganciclovir Solid Organ Transplant Study Group, . (2005). Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients. Clin Pharmacokinet, 44(5), 495–507. https://doi.org/10.2165/00003088-200544050-00003
Wiltshire, Hugh, Sarapee Hirankarn, Colm Farrell, Carlos Paya, Mark D. Pescovitz, Atul Humar, Edward Dominguez, et al. “Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients.Clin Pharmacokinet 44, no. 5 (2005): 495–507. https://doi.org/10.2165/00003088-200544050-00003.
Wiltshire H, Hirankarn S, Farrell C, Paya C, Pescovitz MD, Humar A, et al. Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients. Clin Pharmacokinet. 2005;44(5):495–507.
Wiltshire, Hugh, et al. “Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients.Clin Pharmacokinet, vol. 44, no. 5, 2005, pp. 495–507. Pubmed, doi:10.2165/00003088-200544050-00003.
Wiltshire H, Hirankarn S, Farrell C, Paya C, Pescovitz MD, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B, Freeman R, Heaton N, Valganciclovir Solid Organ Transplant Study Group. Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients. Clin Pharmacokinet. 2005;44(5):495–507.
Journal cover image

Published In

Clin Pharmacokinet

DOI

ISSN

0312-5963

Publication Date

2005

Volume

44

Issue

5

Start / End Page

495 / 507

Location

Switzerland

Related Subject Headings

  • Valganciclovir
  • Prodrugs
  • Pharmacology & Pharmacy
  • Organ Transplantation
  • Models, Biological
  • Middle Aged
  • Male
  • Humans
  • Ganciclovir
  • Female