Adamiszak Arkadiusz, Derwich Katarzyna, Bartkowska-Śniatkowska Alicja, Pietrzkiewicz Krzysztof, Niewiadomska-Wojnałowicz Izabela, Czyrski Andrzej, Jusko William J, Bienert Agnieszka
Department of Pharmacology, Poznan University of Medical Sciences, 60-806 Poznan, Poland.
Doctoral School, Poznan University of Medical Sciences, 60-812 Poznan, Poland.
Pharmaceutics. 2025 Apr 8;17(4):488. doi: 10.3390/pharmaceutics17040488.
: A population pharmacokinetic (popPK) model was used to evaluate fluconazole dosing regimens for spp. prophylaxis in hemato-oncologic pediatric patients. : Data were collected from patients receiving 3-12 mg/kg of fluconazole once daily as a 0.5 or 1 h infusion. Fluconazole concentrations were determined using a validated HPLC-UV method. The popPK model employed non-linear mixed effects modeling using the FOCEI algorithm implemented in nlmixr2. Monte Carlo simulations and probability of target attainment (PTA) analysis were performed in the rxode2 package to investigate dosing recommendations. : Concentration time data from nine patients, aged 7 months to 18 years, with 35 samples, were described by a one-compartment model with first-order elimination and allometric scaling of body weight. Assuming a spp. MIC = 2 mg/L and the ratio of the area under the unbound concentration-time curve at a steady state to the MIC (AUC/MIC) ≥ 100 as the pharmacokinetic/pharmacodynamic (PK/PD) target, the standard dosing regimens reported in the Summary of Product Characteristics (SmPC) did not achieve the target for patients treated with doses < 6 mg/kg. : Hemato-oncologic pediatric patients require increased fluconazole doses to attain therapeutic efficacy. These results warrant clinical validation and should be confirmed by assessing a larger number of patients.
采用群体药代动力学（popPK）模型评估血液肿瘤儿科患者预防感染时氟康唑的给药方案。：数据收集自接受每日一次3 - 12 mg/kg氟康唑、输注时间为0.5或1小时的患者。使用经过验证的高效液相色谱 - 紫外法测定氟康唑浓度。popPK模型采用非线性混合效应模型，使用nlmixr2中实现的FOCEI算法。在rxode2软件包中进行蒙特卡洛模拟和达标概率（PTA）分析，以研究给药建议。：来自9名年龄在7个月至18岁之间的患者的35份浓度 - 时间数据，用具有一级消除和体重异速缩放的单室模型进行描述。假设感染菌的最低抑菌浓度（MIC）= 2 mg/L，稳态下非结合浓度 - 时间曲线下面积与MIC的比值（AUC/MIC）≥ 100作为药代动力学/药效学（PK/PD）目标，产品特性摘要（SmPC）中报告的标准给药方案对于接受剂量< 6 mg/kg治疗的患者未达到目标。：血液肿瘤儿科患者需要增加氟康唑剂量以达到治疗效果。这些结果需要临床验证，并且应该通过评估更多患者来确认。
