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Valacyclovir, an orally administered pro-drug of acyclovir, is utilized in the therapy of herpes simplex and herpes zoster infections. Little data regarding the pharmacokinetics, safety and tolerability are available for pediatric patients. This report describes acyclovir pharmacokinetics following valacyclovir administration in immunocompromised pediatric patients, compares pharmacokinetic parameters following oral valacyclovir and IV acyclovir, and provides a limited assessment of efficacy in the setting of active herpes zoster infection.A total of 37 immunocompromised children were enrolled on one of two studies. Pharmacokinetic data are available for 32 patients following valacyclovir (15 mg/kg) administration, 11 of whom also had pharmacokinetic sampling following IV acyclovir administration. Three patients received valacyclovir as treatment for herpes zoster infections.Mean (±SD) Cmax values for acyclovir following oral valacyclovir were 18.8 ± 7 μM with a total exposure of 4,106 ± 1,519 μM min. The mean bioavailability of acyclovir from valacyclovir was 64%. Grade 1 nausea and emesis, which occurred in five patients was the only valacyclovir-related toxicity. Two of the three patients treated for herpes zoster had complete scabbing of lesions by day 9.Valacyclovir (15 mg/kg) was well tolerated in pediatric patients and demonstrated excellent bioavailability. Consideration should be given to the use of oral valacyclovir for the treatment of herpes zoster in clinically stable pediatric oncology patients. Pediatr Blood Cancer 2008;51:504–508. © 2008 Wiley-Liss, Inc.