Liszka Karolina, Marschollek Paweł, Przystupski Dawid, Frączkiewicz Jowita, Mielcarek-Siedziuk Monika, Olejnik Igor, Gamrot Zuzanna, Haze Natalia, Kwella Agnieszka, Zalewska Paulina, Resztak Matylda, Ussowicz Marek, Kałwak Krzysztof
Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, Borowska 213, 50-556 Wroclaw, Poland.
MonitLab Laboratory, 61-612 Poznan, Poland.
J Fungi (Basel). 2025 Jan 6;11(1):38. doi: 10.3390/jof11010038.
Posaconazole is recommended for prophylaxis in pediatric immunocompromised patients. Due to its variability in bioavailability and drug-to-drug interactions, EBMT recommends regimens based on therapeutic drug monitoring (TDM).
In total, 171 oncohematological pediatric patients on posaconazole prophylaxis were included. Full pharmacokinetic posaconazole profiles were assessed in 51 children. The efficacy and safety of posaconazole was evaluated by measuring the drug concentration, with dose modification attempted in patients with suboptimal results. The influence of modifying factors on the posaconazole plasma concentration (PPC) was investigated.
An insufficient PPC was the main issue, but no significant increase in prophylaxis failure was reported. The modification of the dosage resulted in the optimization of PPC in 50% of patients. No significant correlation between age, gender, diagnosis or the posaconazole dosage and the PPC was found. HCT, total parenteral nutrition and diarrhea were associated with a lower PPC. Hypoalbuminemia was related to both higher and lower PPC. The concomitant administration of specified drugs significantly impacted the PPC.
TDM allows the identification of patients receiving non-optimal treatment and offers an opportunity to improve the efficacy and safety of the therapy. However, further research involving larger patient groups and longer observation periods are needed to determine the optimal dosing and target PPC in pediatric patients.
泊沙康唑被推荐用于儿科免疫功能低下患者的预防治疗。由于其生物利用度的变异性和药物相互作用，欧洲血液和骨髓移植协会（EBMT）推荐基于治疗药物监测（TDM）的治疗方案。
总共纳入了171例接受泊沙康唑预防治疗的儿科肿瘤血液学患者。对51名儿童进行了完整的泊沙康唑药代动力学分析。通过测量药物浓度评估泊沙康唑的疗效和安全性，对结果不理想的患者尝试调整剂量。研究了影响因素对泊沙康唑血浆浓度（PPC）的影响。
主要问题是PPC不足，但未报告预防失败率有显著增加。50%的患者通过调整剂量使PPC达到最佳。未发现年龄、性别、诊断或泊沙康唑剂量与PPC之间存在显著相关性。血细胞比容（HCT）、全胃肠外营养和腹泻与较低的PPC相关。低白蛋白血症与较高和较低的PPC均有关。特定药物的联合使用对PPC有显著影响。
TDM能够识别接受非最佳治疗的患者，并为提高治疗的疗效和安全性提供机会。然而，需要开展涉及更大患者群体和更长观察期的进一步研究，以确定儿科患者的最佳给药剂量和目标PPC。
