Department of Pharmacy, University of Michigan Health System, Ann Arbor, MI, USA.
Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Health System and Medical School, Ann Arbor, MI, USA.
J Antimicrob Chemother. 2017 Oct 1;72(10):2902-2905. doi: 10.1093/jac/dkx228.
Posaconazole is the prophylactic antifungal of choice for patients with haematological malignancies at high risk of invasive fungal infections (IFIs). Studies have demonstrated that subtherapeutic concentrations of posaconazole are associated with breakthrough fungal infections and specific risk factors for subtherapeutic troughs associated with the suspension formulation have been identified. However, these risk factors have not been evaluated in a large patient population with the recently approved tablet formulation.
To determine the risk factors for subtherapeutic posaconazole troughs associated with the tablet formulation in patients receiving posaconazole as IFI prophylaxis.
From 1 February 2013 to 31 March 2015 all posaconazole serum trough concentrations were evaluated. A total of 157 patients receiving posaconazole tablet for prophylaxis during induction therapy for haematological malignancies and allogeneic stem cell transplant recipients with graft-versus-host disease were included for analysis.
Overall, 28 patients (18%) had subtherapeutic troughs (<700 ng/mL). Patients were more likely to have subtherapeutic troughs if they had diarrhoea (n = 24; 83%) (P < 0.001), were receiving a proton pump inhibitor (n = 27; 93%) (P = 0.016) and weighed >90 kg (n = 14; 48%) (P = 0.047).
While the posaconazole tablet has provided more consistent therapeutic concentrations when compared with the suspension there may still be a role for therapeutic drug monitoring (TDM). These results may guide us to a specific population in which TDM is necessary to identify subtherapeutic troughs.
泊沙康唑是血液恶性肿瘤高危侵袭性真菌感染（IFI）患者的首选预防用抗真菌药物。研究表明，泊沙康唑的治疗浓度与突破性真菌感染有关，并且已经确定了与混悬液制剂相关的治疗浓度谷值相关的特定危险因素。然而，这些危险因素尚未在最近批准的片剂制剂的大量患者中进行评估。
确定接受泊沙康唑预防 IFI 的患者中与片剂制剂相关的治疗浓度谷值的泊沙康唑的危险因素。
从 2013 年 2 月 1 日至 2015 年 3 月 31 日，评估了所有泊沙康唑血清谷浓度。共纳入 157 例接受泊沙康唑片剂预防血液恶性肿瘤诱导治疗期间和异基因造血干细胞移植受者移植物抗宿主病的患者进行分析。
总体而言，28 例（18%）患者的谷值浓度较低（<700ng/mL）。如果患者有腹泻（n=24；83%）（P<0.001）、正在接受质子泵抑制剂（n=27；93%）（P=0.016）和体重>90kg（n=14；48%）（P=0.047），则更有可能出现治疗浓度谷值较低的情况。
虽然与混悬液相比，泊沙康唑片剂提供了更一致的治疗浓度，但仍可能需要治疗药物监测（TDM）。这些结果可能指导我们针对特定人群进行 TDM，以确定治疗浓度谷值较低的情况。
