An investigation of the steady-state pharmacokinetics of oral valacyclovir in immunocompromised children.

Author(s): Nadal D, Leverger G, Sokal EM, Floret D, Perel Y, Leibundgut K, Weller S

Affiliation(s): Division of Infectious Diseases, University Children's Hospital of Zurich, CH-8032 Zurich, Switzerland. dnadal@kispi.unizh.ch

Publication date & source: 2002-10-15, J Infect Dis., 186 Suppl 1:S123-30.

Publication type: Clinical Trial; Multicenter Study; Randomized Controlled Trial

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 microg/mL, respectively. Corresponding single dose area-under-curve values were 12.14+/-6.60 and 14.49+/-4.69h microg/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.