Department of Pharmacy Services, West Virginia University Hospitals, Morgantown, WV, USA.
Int J Antimicrob Agents. 2011 Mar;37(3):266-9. doi: 10.1016/j.ijantimicag.2010.11.021. Epub 2011 Jan 13.
This is one of the first studies to report on therapeutic drug monitoring (TDM) of posaconazole (PCZ) for antifungal prophylaxis in patients with acute myelogenous leukaemia or myelodysplastic syndrome outside of the rigours of clinical licencing trials. A number of factors have been identified or proposed as causing poor oral absorption of PCZ. Putative PCZ concentrations have been recommended for TDM (0.5 μg/mL or 0.7 μg/mL). In this study, 19 (90.5%) of 21 patients failed to reach the higher putative target of 0.7 μg/mL, and 16 patients (76.2%) failed to reach the lower target of 0.5 μg/mL. Increasing the dose did not help four of six patients reach target concentrations. Three of the patients developed 'proven' or 'possible' fungal infections, all with PCZ concentrations <0.5 μg/mL. Use of acid-suppressing agents appears to explain some of the poor absorption. TDM of PCZ is warranted in patients receiving this orally administered agent.
这是首批报告之一，内容涉及在急性髓性白血病或骨髓增生异常综合征患者中进行泊沙康唑（PCZ）抗真菌预防治疗的治疗药物监测（TDM），这些患者的情况不在临床试验的严格限制范围内。已经确定或提出了许多导致泊沙康唑口服吸收不良的因素。已经推荐了泊沙康唑的推定浓度用于 TDM（0.5μg/mL 或 0.7μg/mL）。在这项研究中，21 名患者中有 19 名（90.5%）未能达到较高的 0.7μg/mL 推定目标，16 名患者（76.2%）未能达到较低的 0.5μg/mL 目标。增加剂量并不能帮助六名患者中的四名达到目标浓度。三名患者出现了“确诊”或“可能”的真菌感染，所有患者的泊沙康唑浓度均<0.5μg/mL。使用酸抑制药物似乎可以解释部分吸收不良的情况。对于接受这种口服药物的患者，需要进行泊沙康唑 TDM。
