Vanstraelen Kim, Colita Anca, Bica Ana Maria, Mols Raf, Augustijns Patrick, Peersman Nele, Vermeersch Pieter, Annaert Pieter, Spriet Isabel
From the *Clinical Pharmacology and Pharmacotherapy, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, University Hospitals Leuven, Leuven, Belgium; †Pediatric Department, Fundeni Clinical Institute; ‡Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; §Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences; and ¶Clinical Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.
Pediatr Infect Dis J. 2016 Feb;35(2):183-8. doi: 10.1097/INF.0000000000000963.
Antifungal prophylaxis remains challenging in immunocompromised children as no clear consensus has yet been reached about which drug to be used. Posaconazole has a broad spectrum of activity, a favorable safety profile and excellent prophylactic activity in adults. However, a lack of pharmacokinetic studies in pediatric patients hampers routine implementation. This study investigates the pharmacokinetics of a newly introduced posaconazole dosing regimen based on the body surface area in pediatric hematologic patients.
In this prospective pharmacokinetic study, 8 blood samples were taken during 1 dosing interval at steady state in children aged 13 years or younger with hematologic malignancy, who were treated prophylactically with posaconazole oral suspension at a dose of 120 mg/m 3 times daily. Posaconazole plasma concentrations were determined using high-performance liquid chromatography fluorescence detection.
One hundred twelve samples were taken from 14 patients with a mean age of 6.7 ± 2.8 years. A median posaconazole daily dose of 100.0 mg (77.3-100.0) 3 times daily (tid), corresponding to a median of 117.9 mg/m (112.2-120.4) tid, resulted in mean trough posaconazole plasma concentrations of 0.85 ± 0.56 mg/L. Pharmacokinetic analysis revealed a clearance of 0.8 L/(h kg) (0.5-1.4). No invasive fungal infections or adverse events were encountered during treatment.
Posaconazole is a promising antifungal agent to be used prophylactically in hematologic patients aged 13 years or younger. Administering posaconazole oral suspension in a dosage of 120 mg/m tid results in adequate posaconazole plasma exposure, without significant adverse events.
对于免疫功能低下的儿童，抗真菌预防治疗仍然具有挑战性，因为对于使用哪种药物尚未达成明确共识。泊沙康唑具有广泛的活性谱、良好的安全性和在成人中出色的预防活性。然而，儿科患者缺乏药代动力学研究阻碍了其常规应用。本研究调查了一种新引入的基于体表面积的泊沙康唑给药方案在儿科血液学患者中的药代动力学。
在这项前瞻性药代动力学研究中，对13岁及以下患有血液系统恶性肿瘤且接受泊沙康唑口服混悬液预防性治疗（剂量为120mg/m³，每日3次）的儿童，在稳态下的1个给药间隔内采集8份血样。使用高效液相色谱荧光检测法测定泊沙康唑血浆浓度。
从14名平均年龄为6.7±2.8岁的患者中采集了112份样本。泊沙康唑每日中位剂量为100.0mg（77.3 - 100.0），每日3次（tid），相当于中位剂量为117.9mg/m（112.2 - 120.4）tid，导致泊沙康唑血浆平均谷浓度为0.85±0.56mg/L。药代动力学分析显示清除率为0.8L/（h·kg）（0.5 - 1.4）。治疗期间未发生侵袭性真菌感染或不良事件。
泊沙康唑是一种有前景的抗真菌药物，可用于13岁及以下血液学患者的预防性治疗。以120mg/m³ tid的剂量给予泊沙康唑口服混悬液可使泊沙康唑血浆暴露量充足，且无明显不良事件。
