Sienkiewicz-Oleszkiewicz Beata, Urbańczyk Kamila, Stachowiak Mateusz, Rodziewicz Anna, Zięba Aleksander, Kałwak Krzysztof, Wiela-Hojeńska Anna
1Department of Clinical Pharmacology, Faculty of Pharmacy, Wrocław Medical University, 211a Borowska St., 50-556 Wrocław, Poland.
2Department of Paediatric Bone Marrow Transplantation, Oncology and Hematology, Wrocław Medical University, 213 Borowska St., 50-556 Wrocław, Poland.
Indian J Hematol Blood Transfus. 2019 Oct;35(4):699-706. doi: 10.1007/s12288-019-01134-5. Epub 2019 May 14.
The aim of this study was to determine the impact of ABCB1 polymorphism, BMI, age and drug co-administration on safety and efficiency of posaconazole (PCZ) oral suspension treatment in children with hematological diseases. Seventy children were included in the study. ABCB1 polymorphism in fifty-eight children was determined using a PCR-RFLP method. A protocol with data on the health condition, treatment and adverse events (AE), as well as a survey on treatment tolerance for the legal guardians was evaluated. Liver function tests were observed for the first 20 days, and AE during the complete medication period. For statistical analysis a χ test with Yates's correction, a Pearson's or Spearman's correlation test was performed ( < 0.05). Genetic testing showed 24% CC, 46% CT and 30% of TT variants. PCZ prophylaxis failed in twenty cases, where change in prophylactic treatment was needed. Fifty-two children suffered from at least one mild to moderate adverse event. Sixty-five legal guardians completed the survey, most of them reported the treatment to be well tolerated. ABCB1 polymorphism had no impact on AE occurrence and posaconazole prophylaxis efficiency. Age influenced the number of gastrointestinal ( = 0.02), visual ( = 0.05), neurological ( = 0.01), dermatological ( = 0.002) and flu-like ( = 0.02) complications. AST ( = 0.03) and LDH ( = 0.008) activity presented age dependency. The concomitant use of proton pump inhibitors (PPI) had impact on liver health parameters elevation ( = 0.009) and circulatory system complications ( = 0.008). High incidence of mild to moderate AE, and other factors influencing PCZ pharmacokinetics (PPI co-administration, obesity), suggest a need for careful pediatric onco-hematology patient evaluation.
本研究的目的是确定ABCB1基因多态性、体重指数（BMI）、年龄及药物联合使用对泊沙康唑（PCZ）口服混悬液治疗血液系统疾病患儿的安全性和有效性的影响。70名儿童纳入本研究。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法测定58名儿童的ABCB1基因多态性。评估一份包含健康状况、治疗及不良事件（AE）数据的方案，以及对法定监护人进行的治疗耐受性调查。在开始的20天观察肝功能检查结果，并在整个用药期间观察不良事件。进行统计学分析时采用了经Yates校正的χ检验、Pearson或Spearman相关性检验（P<0.05）。基因检测显示CC变异型占24%，CT变异型占46%，TT变异型占30%。20例患儿的PCZ预防治疗失败，需要更换预防治疗方案。52名儿童至少发生了1次轻度至中度不良事件。65名法定监护人完成了调查，其中大多数人报告治疗耐受性良好。ABCB1基因多态性对不良事件的发生及泊沙康唑预防治疗的有效性无影响。年龄影响胃肠道（P=0.02）、视觉（P=0.05）、神经（P=0.01）、皮肤（P=0.002）及流感样（P=0.02）并发症的数量。谷草转氨酶（AST，P=0.03）和乳酸脱氢酶（LDH，P=0.008）活性呈现年龄依赖性。质子泵抑制剂（PPI）的联合使用对肝脏健康参数升高（P=0.009）及循环系统并发症（P=0.008）有影响。轻度至中度不良事件的高发生率以及其他影响PCZ药代动力学的因素（PPI联合使用、肥胖）表明，需要对儿科肿瘤血液科患者进行仔细评估。
