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

作者：David W. Kimberlin, Richard F. Jacobs, S Weller, Jan‐Stefan van der Walt, Catherine K. Heitman, Choy Man, John S. Bradley · 发表于：Clinical Infectious Diseases · 年份：2009 · DOI：10.1086/649212 · 被引用次数：63 · 研究领域：Herpesvirus Infections and Treatments、Cytomegalovirus and herpesvirus research、Virus-based gene therapy research

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), whereas children 1 through 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 (C(max)) of acyclovir and the area under the concentration-time curve from time zero extrapolated to infinity (AUC(0-infinity)) 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 C(max) and AUC(0-infinity). Among infants 1 through 2 months of age receiving 25 mg/kg, the mean AUC(0-infinity) and C(max) were higher ( approximately 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...