Heinz W J, Einsele H, Helle-Beyersdorf A, Zirkel J, Grau A, Schirmer D, Lenker U, Klinker H
Department of Internal Medicine II, University of Wuerzburg Medical Center, Wuerzburg, Germany.
Transpl Infect Dis. 2013 Oct;15(5):449-56. doi: 10.1111/tid.12108. Epub 2013 Jul 25.
Posaconazole is recommended for prophylaxis of fungal infections and for salvage therapy of invasive aspergillosis after stem cell transplantation. An impact of drug concentration on efficacy has been suggested.
In this study, we investigated serum levels of posaconazole in 262 samples from 64 allogeneic stem cell recipients.
A high degree of interindividual variation was observed. Concentrations were significantly higher for male patients compared with female patients (median 570 and 426 ng/mL, respectively), but no differences for age or dosing groups (400 mg twice daily [BID] or 200 mg three times a day) could be detected. The predictive value of the first determined posaconazole concentration in steady state and of a concentration >500 and 700 ng/mL at any time was evaluated, compared with patients with a first level <300 ng/mL (mean 10.3%, median 0%).
In patients receiving 400 mg BID, the mean rate of serum levels >500 ng/mL in subsequent determinations was higher, if the first serum concentration during steady state was >300 ng/mL (mean 61.1%, median 60%, P = 0.002) or >500 ng/mL (67.7%, median 75%, P = 0.002). Based on this retrospective analysis, a posaconazole serum concentration >500 ng/mL at any time point might also help to predict sufficient drug concentrations.
泊沙康唑被推荐用于预防真菌感染以及异基因干细胞移植后侵袭性曲霉病的挽救治疗。已有研究表明药物浓度对疗效有影响。
在本研究中，我们检测了64例异基因干细胞移植受者的262份样本中的泊沙康唑血清水平。
观察到个体间存在高度差异。男性患者的浓度显著高于女性患者（中位数分别为570和426 ng/mL），但在年龄或给药组（每日两次400 mg或每日三次200 mg）之间未检测到差异。将首次测定的稳态泊沙康唑浓度以及任何时间浓度>500和700 ng/mL的预测价值与首次水平<300 ng/mL的患者（均值10.3%，中位数0%）进行了比较。
在接受每日两次400 mg给药的患者中，如果稳态时首次血清浓度>300 ng/mL（均值61.1%，中位数60%，P = 0.002）或>500 ng/mL（67.7%，中位数75%，P = 0.002），后续测定中血清水平>500 ng/mL的平均发生率更高。基于这项回顾性分析，任何时间点泊沙康唑血清浓度>500 ng/mL可能也有助于预测药物浓度是否充足。
