Cumpston Aaron, Caddell Ryan, Shillingburg Alexandra, Lu Xiaoxiao, Wen Sijin, Hamadani Mehdi, Craig Michael, Kanate Abraham S
Department of Pharmacy, West Virginia University Hospitals, Morgantown, West Virginia, USA Osborn Hematopoietic Malignancy and Transplantation Program, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia, USA
Department of Pharmacy, West Virginia University Hospitals, Morgantown, West Virginia, USA.
Antimicrob Agents Chemother. 2015 Aug;59(8):4424-8. doi: 10.1128/AAC.00581-15. Epub 2015 May 18.
Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT [QTc] interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp (n = 118) or PCZ-tab (n = 32) and had PCZ Css assessment after at least 7 days of therapy were eligible. The median Css in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group (P < 0.0001). The percentages of patients achieving the target goal of ≥700 ng/ml were 17% versus 97%, respectively (P < 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% (n = 3) and 17% (n = 2), respectively (P = 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% (n = 8) and 3% (n = 1), respectively (P = 0.68). We conclude that the use of PCZ-tab was associated with higher Css and with the probability of achieving therapeutic goals without worsening of adverse effects.
泊沙康唑（PCZ）已被批准用于预防高危患者的侵袭性真菌病，有口服混悬液剂型（PCZ-susp）和缓释片剂（PCZ-tab）两种市售剂型。我们评估了150例髓系恶性肿瘤患者中，根据给药剂型分层的PCZ血清稳态浓度（Css），以用于抗真菌预防。主要结局是达到≥700 ng/ml目标Css的达成率。次要结局包括毒性评估（肝毒性和校正QT [QTc]间期延长）以及突破性真菌感染。接受PCZ-susp（n = 118）或PCZ-tab（n = 32）治疗且在至少7天治疗后进行PCZ Css评估的患者符合条件。PCZ-susp组的Css中位数为390 ng/ml（范围为51至1870 ng/ml；均值为436 ng/ml），而PCZ-tab组为1740 ng/ml（范围为662至3350 ng/ml；均值为1781 ng/ml）（P < 0.0001）。达到≥700 ng/ml目标的患者百分比分别为17%和97%（P < 0.0001）。每组各有1例患者发生肝毒性（2级或更高）。PCZ-susp组有32例患者和PCZ-tab组有12例患者可进行QTc间期测量，2级或更高的间期延长分别见于9%（n = 3）和17%（n = 2）的患者（P = 0.6）。PCZ-susp组和PCZ-tab组的突破性真菌感染分别为7%（n = 8）和3%（n = 1）（P = 0.68）。我们得出结论，使用PCZ-tab与更高的Css相关，且有实现治疗目标而不加重不良反应的可能性。
