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Pharmacokinetic Profile of Ganciclovir After its Oral Administration and From its Prodrug, Valganciclovir, in Solid Organ Transplant Recipients

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Abstract

Background

Valganciclovir (Valcyte/sR) has recently been approved for the prevention of cytomegalovirus (CMV) disease in high-risk (CMV donor positive [D+1/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®, lOOOmg 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 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 μg · h/mL and 28.0 ± 10.9 μg · 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 μg · 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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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

This study was funded by Hoffman-La Roche Ltd, Basel, Switzerland. Hugh Wiltshire is an employee of the sponsor. Mark Pescovitz has received honoraria for speaking and is a consultant to the sponsor. Atul Humar is a consultant for the sponsor. Barbara Alexander, Emily Blumberg and Richard Freeman have received honoraria for speaking for the sponsor.

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Authors and Affiliations

  1. Roche Products Ltd, 40 Broadwater Road, Welwyn Garden City, HERTS AL7 3AY, UK

    Hugh Wiltshire

  2. GloboMax — a division of ICON plc, Marlow, UK

    Sarapee Hirankarn & Colm Farrell

  3. Mayo Clinic, Rochester, New York, USA

    Carlos Paya

  4. Departments of Surgery/Microbiology/Immunology, Indiana University, Indianapolis, Indiana, USA

    Mark D. Pescovitz

  5. Toronto General Hospital, Toronto, Ontario, Canada

    Atul Humar

  6. University of Nebraska Medical Center, Omaha, Nebraska, USA

    Edward Dominguez

  7. University of Texas Health Science Center, San Antonio, Texas, USA

    Kenneth Washburn

  8. Hospital of the University of Pennsylvania, Philadelphia, Pennsylvannia, USA

    Emily Blumberg

  9. Duke University Medical Center, Durham, North Carolina, USA

    Barbara Alexander

  10. New England Medical Center, Boston, Massachusetts, USA

    Richard Freeman

  11. King’s College, London, UK

    Nigel Heaton

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  1. Hugh Wiltshire
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  2. Sarapee Hirankarn
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Corresponding author

Correspondence to Hugh Wiltshire.

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Wiltshire, H., Hirankarn, S., Farrell, C. et al. Pharmacokinetic Profile of Ganciclovir After its Oral Administration and From its Prodrug, Valganciclovir, in Solid Organ Transplant Recipients. Clin Pharmacokinet 44, 495–507 (2005). https://doi.org/10.2165/00003088-200544050-00003

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  • DOI: https://doi.org/10.2165/00003088-200544050-00003

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