Pharmacokinetics and Safety of Extemporaneously Compounded Valacyclovir Oral Suspension in Pediatric Patients from 1 Month through 11 Years of Age

• Published in: Clinical infectious diseases Vol. 50; no. 2; pp. 221 - 228
• Main Authors: Kimberlin, David W., Jacobs, Richard F., Weller, Stephen, van der Walt, Jan-Stefan, Heitman, Catherine K., Man, Choy Y., Bradley, John S.
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 15.01.2010; University of Chicago Press; Oxford University Press
• Subjects: Acyclovir - analogs & derivatives; Acyclovir - pharmacokinetics; Acyclovir - therapeutic use; Administration, Oral; Age groups; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - pharmacokinetics; Antiviral Agents - therapeutic use; ARTICLES AND COMMENTARIES; Babies; Bioavailability; Biological and medical sciences; Chemical suspensions; Chickenpox; Child; Child, Preschool; Children; Dosage; Drug dosages; Female; Herpes simplex virus; Herpes viruses; Herpesviridae Infections - drug therapy; Herpesvirus; Humans; Infant; Infants; Infections; Infectious diseases; Male; Medical sciences; Medical screening; Pharmacokinetics; Pharmacology. Drug treatments; Risk factors; Simplexvirus; Suspensions; Valine - analogs & derivatives; Valine - pharmacokinetics; Valine - therapeutic use; Varicella-zoster virus; Human; Acyclic nucleoside; Purine nucleoside; Oral administration; Valaciclovir; Suspension; Prodrug; Infection; Nucleoside analog; Antiviral; Pharmacokinetics; Child; Age; DNA polymerase inhibitor
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/649212

Background Valacyclovir provides enhanced acyclovir bioavailability in adults, but limited data are available in children. Methods Children 1 month through 5 years of age with or at risk for herpesvirus infection received a single 25 mg/kg dose of extemporaneously compounded valacyclovir oral suspension (n = 57), whereaschildren1through 11 years of age received 10 mg/kg valacyclovir oral suspension twice daily for 3–5 days (herpes simplex virus infection) (n = 28) or 20 mg/kg 3 times daily for 5 days (varicella-zoster virus infection) (n = 27). Blood samples for pharmacokinetic analysis were collected during the 6 h after the first dose. Safety was monitored throughout the studies. Results Dose proportionality in the maximum observed concentration (Cmax) of acyclovir and the area under the concentration-time curve from time zero extrapolated to infinity (AUC0−∞) existed across the 10 to 20 mg/kg valacyclovir dose range. For children 2 through 5 years of age, an increase in dose from 20 to 25 mg/kg resulted in near doubling of the Cmax and AUC0−∞. Among infants 1 through 2 months of age receiving 25 mg/kg, the mean AUC0−∞ and Cmax were higher (∼60% and 30%, respectively) than those among older infants and children receiving the same dose. Valacyclovir oral suspension was well tolerated. No clinically significant trends were noted in clinical chemical, hematologic, or urinalysis values from screening to follow-up. Conclusions Among children 3 months through 11 years of age, the 20 mg/kg dose of this formulation of valacyclovir oral suspension produces favorable acyclovir blood concentrations and is well tolerated. A dosing recommendation cannot be made for infants <3 months of age because of decreased clearance in this age group. Trial registration ClinicalTrials.gov identifier: NCT00297206.