Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children
Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children
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DOI：
10.1128/aac.01427-16
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发表时间：
2016-12-01
影响因子：
4.9
通讯作者：
Hope, William W.
中科院分区：
文献类型：
--
作者：
Lestner, Jodi M.;Groll, Andreas H.;Hope, William W.
脂质体两性霉素B （LAmB）广泛应用于成人和儿童侵袭性真菌病（IFD）的治疗。相对有限的药代动力学（PK）数据表明，儿童达到与成人相当的全身药物暴露的最佳剂量。我们的目的是描述LAmB在1至17岁疑似或记录IFD的儿童中的药代动力学。35名儿童接受每日2.5至10 mg kg（-1）剂量的LAmB治疗。在接受第一次剂量后24小时（n = 35例患者）和治疗最后一天（n = 25例患者），在基线和0.5- 2.0 h间隔取样。采用高效液相色谱法测定羔羊肉含量。探讨了药物暴露与毒性发展的关系。在治疗过程中观察到PK的演变，导致一定比例的患者（n = 13）在治疗过程后期具有显著较高的最大血清浓度（C-max）和0-24 h浓度-时间曲线下面积（AUC(0-24)），没有药物积累的证据（槽血药浓度积累比）
Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg(-1) daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (n = 35 patients) and on the final day of therapy (n = 25 patients). LAmB was measured using high-performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. An evolution in PK was observed during the course of therapy, resulting in a proportion of patients (n = 13) having significantly higher maximum serum concentrations (C-max) and areas under the concentration-time curve from 0 to 24 h (AUC(0-24)) later in the course of therapy, without evidence of drug accumulation (trough plasma concentration accumulation ratio of