Peled Orit, Berkovitch Matitiahu, Rom Eran, Bilavsky Efraim, Bernfeld Yael, Dorfman Lev, Pappo Adi, Ziv-Baran Tomer, Brandriss Nurit, Bar-Haim Adina, Amir Jacob, Ashkenazi-Hoffnung Liat
From the *Department of Pharmacy, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; ‡Clinical Pharmacology and Toxicology Unit, Assaf Harofeh Medical Center, Zriffin, Israel; §Department of Pediatrics C, Schneider Children's Medical Center of Israel, Petach Tikva, Israel; ¶Department of Epidemiology and Preventive Medicine, School of Public Health, Tel Aviv University, Tel Aviv, Israel; and ‖Biochemistry Laboratory, Assaf Harofeh Medical Center, Zriffin, Israel.
Pediatr Infect Dis J. 2017 Aug;36(8):745-750. doi: 10.1097/INF.0000000000001595.
Valganciclovir is extensively used for prophylaxis and treatment of cytomegalovirus (CMV) infection in solid-organ transplant recipients. However, pharmacokinetic data in children are scarce, and the pediatric dosing regimen is uncertain. This study sought to prospectively evaluate the pharmacokinetic profile, the clinical efficacy and safety of oral valganciclovir in pediatric transplant recipients and compare different dosing regimens.
The cohort included solid-organ transplant recipients treated with valganciclovir for CMV prophylaxis in 2014-2015 at a tertiary pediatric medical center. All received a weight-based once-daily oral dose of 17 mg/kg. Ganciclovir concentrations were measured and the area under the curve (AUC0-24) was calculated.
Thirteen children of median age 7.3 years (interquartile range, 2.2-11.6) were included. Median ganciclovir AUC0-24 was 21.0 mcg·h/mL (interquartile range, 17.1-39.8); 10 patients (77%) attained AUC0-24 <40 mcg·h/mL. Exposure to ganciclovir was about 2-fold lower in young children (<9 years old; P = 0.01) and children with low body surface area (BSA; <0.7 m; P = 0.006) than in their counterparts. Significantly lower doses were recommended with our weight-based protocol than with the manufacturer-recommended BSA- and glomerular filtration rate-based protocol (P = 0.002), reaching a 3-fold difference in infants. No evidence of CMV viremia or disease was observed while prophylaxis was given.
The weight-based regimen of 17 mg/kg/dose oral valganciclovir results in relatively low ganciclovir exposure, especially in young children with low BSA, yet showed satisfactory clinical efficacy for CMV prophylaxis. The manufacturer's dosing recommendation appears to result in supratherapeutic ganciclovir concentrations. Further studies are needed to establish target AUCs and valganciclovir dosing for CMV prophylaxis in pediatric transplant recipients.
缬更昔洛韦广泛用于实体器官移植受者巨细胞病毒（CMV）感染的预防和治疗。然而，儿童的药代动力学数据稀缺，儿科给药方案尚不确定。本研究旨在前瞻性评估口服缬更昔洛韦在儿科移植受者中的药代动力学特征、临床疗效和安全性，并比较不同给药方案。
该队列包括2014年至2015年在一家三级儿科医疗中心接受缬更昔洛韦预防CMV治疗的实体器官移植受者。所有患者均接受基于体重的每日一次口服剂量17mg/kg。测量更昔洛韦浓度并计算曲线下面积（AUC0-24）。
纳入了13名中位年龄为7.3岁（四分位间距，2.2-11.6）的儿童。更昔洛韦AUC0-24中位数为21.0mcg·h/mL（四分位间距，17.1-39.8）；10名患者（77%）的AUC0-24<40mcg·h/mL。幼儿（<9岁；P=0.01）和低体表面积（BSA；<0.7m；P=0.006）儿童的更昔洛韦暴露量比相应儿童低约2倍。与制造商推荐的基于BSA和肾小球滤过率的方案相比，我们基于体重的方案推荐的剂量显著更低（P=0.002），婴儿中的差异达3倍。预防期间未观察到CMV病毒血症或疾病的证据。
口服缬更昔洛韦基于体重的方案17mg/kg/剂量导致相对较低的更昔洛韦暴露，尤其是在低BSA的幼儿中，但对CMV预防显示出令人满意的临床疗效。制造商的给药建议似乎导致更昔洛韦浓度超治疗水平。需要进一步研究以确定儿科移植受者CMV预防的目标AUC和缬更昔洛韦给药方案。
