Department of Pediatrics, University of Alabama, Birmingham, AL 35233, USA.
Clin Infect Dis. 2010 Jan 15;50(2):221-8. doi: 10.1086/649212.
Valacyclovir provides enhanced acyclovir bioavailability in adults, but limited data are available in children.
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.
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.
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 .
伐昔洛韦可提高成人阿昔洛韦的生物利用度，但儿童的相关数据有限。
患有疱疹病毒感染或有感染风险的 1 个月至 5 岁儿童（n=57）单次给予 25mg/kg 剂量的临时配制的伐昔洛韦口服混悬剂；1 至 11 岁儿童（n=28）接受 10mg/kg 伐昔洛韦口服混悬剂，每日两次，持续 3-5 天（单纯疱疹病毒感染）；或 20mg/kg，每日 3 次，持续 5 天（水痘带状疱疹病毒感染）（n=27）。首次给药后 6 小时内采集血样进行药代动力学分析。整个研究过程中监测安全性。
在 10 至 20mg/kg 伐昔洛韦剂量范围内，观察到阿昔洛韦的最大浓度（C(max)）和从零时间外推至无穷大的浓度-时间曲线下面积（AUC(0-infinity)）与剂量呈比例关系。对于 2 至 5 岁的儿童，将剂量从 20mg/kg 增加到 25mg/kg 导致 C(max)和 AUC(0-infinity)几乎增加了一倍。在接受 25mg/kg 剂量的 1 至 2 个月龄婴儿中，AUC(0-infinity)和 C(max)均较高（分别约为 60%和 30%），高于接受相同剂量的较大婴儿和儿童。伐昔洛韦口服混悬剂耐受良好。从筛查到随访，未观察到临床化学、血液学或尿液分析值有临床意义的趋势。
在 3 个月至 11 岁的儿童中，该配方的伐昔洛韦口服混悬剂 20mg/kg 剂量可产生良好的阿昔洛韦血药浓度，且耐受良好。由于该年龄组清除率降低，因此不能推荐给 <3 个月龄的婴儿使用。
ClinicalTrials.gov 标识符：NCT00297206 。
