Fluconazole loading dose pharmacokinetics and safety in infants.
Fluconazole loading dose pharmacokinetics and safety in infants.
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DOI：
10.1097/inf.0b013e318202cbb3
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发表时间：
2011-05
期刊：
影响因子：
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通讯作者：
Benjamin DK Jr
中科院分区：
文献类型：
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作者：
Piper L;Smith PB;Hornik CP;Cheifetz IM;Barrett JS;Moorthy G;Hope WW;Wade KC;Cohen-Wolkowiez M;Benjamin DK Jr
背景：侵袭性念珠菌病是危重婴儿发病和死亡的主要原因。及时给予氟康唑并达到治疗目标（0至24小时曲线下面积> 400 mg* h/L）可改善念珠菌病患者的预后。建议老年患者使用氟康唑负荷剂量，但尚未在婴儿中进行评估。我们试图确定氟康唑负荷剂量在有侵袭性真菌感染风险的婴儿中的药代动力学和安全性。方法：在这项开放标签研究中，我们招募了 10 名< 60 天的疑似全身真菌感染的住院婴儿； 9 名患者接受了 25 mg/kg 氟康唑负荷剂量，随后每 24 小时接受 12 mg/kg 维持剂量，持续 4 天。血浆样本是在负荷剂量和稳态剂量（剂量 3-5）后获得的。我们使用 1 室模型拟合数据来估计药代动力学指数。结果：从 8 名婴儿（中位出生后年龄，16 天 [四分位间距，13-32] 和中位胎龄，37 周 [35-38]）获得的 57 个药物浓度的数据显示，该人群中 0 至 24 小时曲线下面积 (mg* h/L) 的中位氟康唑面积为 479 （347–496）。接受负荷剂量的 8 名婴儿中，5 名（63%）在给药第一天就达到了治疗目标，所有婴儿的氟康唑 24 小时谷浓度均> 8 μg/mL。没有不良事件被认为与氟康唑治疗有关。结论：氟康唑负荷剂量（25 mg/kg）对于这一小群幼儿来说是安全的，并且比传统剂量更快地达到治疗目标。
Background:Invasive candidiasis is a leading cause of morbidity and mortality in critically ill infants. Prompt administration of fluconazole and achievement of the therapeutic target (area under the curve 0 to 24 hours> 400 mg* h/L) improve outcomes in candidemic patients. A loading dose of fluconazole is advised for older patients but has not been evaluated in infants. We sought to determine the pharmacokinetics and safety of a fluconazole loading dose in infants at risk for invasive fungal infection.Methods:We enrolled 10 hospitalized infants< 60 days old with suspected systemic fungal infection in this open-label study; 9 received a 25-mg/kg fluconazole loading dose followed by a maintenance dose of 12 mg/kg every 24 hours for 4 additional days. Plasma samples were obtained following the loading and steady-state doses (doses 3–5). We used a 1-compartment model to fit the data to estimate pharmacokinetic indices.Results:Data from 57 drug concentrations obtained from 8 infants (median postnatal age, 16 days [interquartile range, 13–32] and median gestational age, 37 weeks [35–38]) showed that the median fluconazole area under the curve 0 to 24 hours (mg* h/L) in this population was 479 (347–496). Of the 8 infants who received the loading dose, 5 (63%) achieved the therapeutic target on the first day of dosing, and all infants achieved a fluconazole 24-hour trough concentration> 8 μg/mL. No adverse events were thought to be related to fluconazole therapy.Conclusions:A loading dose of fluconazole (25 mg/kg) was safe in this small cohort of young infants and achieved the therapeutic target more rapidly than traditional dosing.