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An Investigation of the Steady-State Pharmacokinetics of Oral Valacyclovir in Immunocompromised Children

Nadal, David ; Leverger, Guy ; Sokal, Etienne M. ; Floret, Daniel ; Perel, Yves ; Leibundgut, Kurt ; Weller, Stephen

In: The Journal of Infectious Diseases, 2002, vol. 186, no. Supplement_1, p. S123-S130

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    Titre
    • An Investigation of the Steady-State Pharmacokinetics of Oral Valacyclovir in Immunocompromised Children
    Auteur
    • Nadal, David. Division of Infectious Diseases, University Children's Hospital of Zurich, Zurich, and
    • Leverger, Guy. Unit of Hematology and Oncology, Department of Pediatrics, Children's Hospital Armand Trousseau, Paris
    • Sokal, Etienne M.. Department de Paediatrie, Université Catholique de Louvain, Brussels, Belgium
    • Floret, Daniel. Service d'Urgence et de Réanimation Pédiatrique, Hôpital Edouard Herriot, Lyon, and
    • Perel, Yves. Unit of Hematology and Oncology, Department of Pediatrics, Children's Hospital, Groupe Hospitalier Pellegrin, Bordeaux, France
    • Leibundgut, Kurt. Department of Pediatrics, Inselspital, University of Bern, Bern, Switzerland
    • Weller, Stephen. GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • The Journal of Infectious Diseases, 2002, vol. 186, no. Supplement_1, p. S123-S130. The University of Chicago Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:303575
    Summary
    Valacyclovir was administered to 28 immunocompromised children (ages 5-12 years) to obtain preliminary pharmacokinetic and safety information. Patients were randomized to valacyclovir regimens of 250 mg (9.4-13.3 mg/kg) or 500 mg (13.9-27.0 mg/kg) twice daily or 500 mg (13.2-21.7 mg/kg) 3 times a day. Acyclovir pharmacokinetics were evaluated at steady state. Valacyclovir was rapidly absorbed and converted to acyclovir. Mean (±SD) acyclovir peak concentrations from 250 mg and 500 mg valacyclovir were 4.11±1.41 and 5.19±1.96 μg/mL, respectively. Corresponding single dose area-under-curve values were 12.14±6.60 and 14.49±4.69h×μg/mL. By using historical data for intravenous acyclovir as reference, the overall estimate of acyclovir bioavailability from valacyclovir was 48%, 2- to 4-fold greater than for oral acyclovir. In general, adverse events were not attributable to valacyclovir and were consistent with disease-related expectations and concomitant therapies. Dosage options for using valacyclovir in children are discussed