Pharmacokinetics and safety of posaconazole intravenous solution and powder for oral suspension in children with neutropenia: an open-label, sequential dose-escalation trial
Pharmacokinetics and safety of posaconazole intravenous solution and powder for oral suspension in children with neutropenia: an open-label, sequential dose-escalation trial
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DOI：
10.1016/j.ijantimicag.2020.106084
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发表时间：
2020-09-01
影响因子：
10.8
通讯作者：
Bruno, Christopher J.
中科院分区：
文献类型：
--
作者：
Groll, Andreas H.;Abdel-Azim, Hisham;Bruno, Christopher J.
泊沙康唑被批准作为静脉(IV)溶液和两种不同的口服制剂(混悬液和改进的生物利用度片剂)用于成人。关于泊沙康唑在儿童中的药代动力学(PK)、剂量和安全性的数据有限。一种新型的口服混悬粉(PFS)提供了用于儿童体重给药的片剂的生物利用度。一项非随机的OpenLabel序贯剂量递增1b期试验评估了泊沙康唑IV和PFS在2至17岁确诊或预期患有中性粒细胞减少症的儿童中的PK和安全性(ClinicalTrials.gov，NCT02452034；MSD方案编号，MK-5592-P097)。受试者接受泊沙康唑静脉注射3.5、4.5或6.0 mg/kg/d，疗程=10天，并选择改用泊沙康唑PFS，剂量相同，剂量为500 ng/mL。在所有剂量的所有年龄组中，PFS导致泊沙康唑的暴露低于IV。泊沙康唑IV和PFS耐受性良好，安全性与报道的成人用药相似。泊沙康唑在静脉注射和PFS注射后的PK有很好的数据特征，并使选择适当的儿科剂量成为可能。两种制剂的耐受性都很好，在安全性方面没有剂量、暴露或年龄方面的差异。(C)2020爱思唯尔有限公司和国际抗菌化疗学会。版权所有。
Posaconazole is approved for use in adults as an intravenous (IV) solution and two different oral formulations (a suspension and an improved bioavailability tablet). Data on the pharmacokinetics (PK), dosing and safety of posaconazole in children are limited. A novel powder for oral suspension (PFS) offers the bioavailability of the tablet formulated for weight-based dosing in children. A non-randomised, openlabel, sequential dose-escalation, phase 1b trial evaluated the PK and safety of posaconazole IV and PFS in children aged 2 to 17 years with documented or expected neutropenia (ClinicalTrials.gov, NCT02452034; MSD protocol number, MK-5592-P097). Participants received posaconazole IV 3.5, 4.5 or 6.0 mg/kg/d for >= 10 days, with an option to switch to posaconazole PFS at the identical dose for = 500 ng/mL. PFS resulted in lower posaconazole exposures than IV across age groups at all doses. Posaconazole IV and PFS were well tolerated and had safety profiles similar to those reported for adults. Posaconazole PK following IV and PFS administration was well characterised by the data and enable selection of appropriate paediatric doses. Both formulations were well tolerated without dose-, exposure- or age-related differences in the safety profiles. (c) 2020 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.