Department of Clinical Hematology, Institute J. Bordet, Brussels, Belgium.
Antimicrob Agents Chemother. 2012 Dec;56(12):6298-303. doi: 10.1128/AAC.01177-12. Epub 2012 Oct 1.
Posaconazole is a broad-spectrum triazole antifungal available as an oral suspension. Pharmacokinetic data showed a high variability of plasma posaconazole concentrations (PPCs) in patients, suggesting a potential interest in drug monitoring. The aim of our prospective study was to measure the PPCs in prophylactically treated patients to evaluate the impact of different factors on these concentrations. In 40 patients treated prophylactically with posaconazole for acute myeloid leukemia or myelodysplastic syndrome between February 2009 and August 2010, PPCs were measured at day 7 of treatment and then twice weekly. Demographic data, clinical data (including gastrointestinal disorders, comedications, and treatment compliance), caloric and fat intake, and biological data were collected and evaluated. We obtained 275 measurements of PPCs, with a median of 430 ng/ml. PPCs were significantly lower in patients with mucositis (P < 0.001), nausea (P = 0.03), diarrhea (P = 0.03), or vomiting (P = 0.05). PPCs were higher in patients with a higher caloric intake (P = 0.02), while the proportion of fat intake had no influence on PPCs (P = 0.84). The concomitant use of proton pump inhibitors decreased the PPCs (P = 0.02), while the use of tacrolimus increased the PPC (P = 0.03). In the multivariate analysis, the factors influencing the PPCs independently were the concomitant use of tacrolimus (P < 0.001), the presence of mucositis (P = 0.01), and food intake (P = 0.02). Our study confirmed the high variability of posaconazole bioavailability and showed the significant influence of gastrointestinal disorders, food intake, and concomitant medication on the PPCs. However, the optimal PPCs still remain to be defined and correlated with clinical efficacy.
泊沙康唑是一种广谱三唑类抗真菌药，有口服混悬液剂型。药代动力学数据显示，接受泊沙康唑预防性治疗的患者其血浆泊沙康唑浓度（PPC）变异性很大，提示药物监测可能具有潜在意义。我们的前瞻性研究旨在测量预防性接受泊沙康唑治疗的患者的 PPC，以评估不同因素对这些浓度的影响。在 2009 年 2 月至 2010 年 8 月期间，40 例接受泊沙康唑预防性治疗的急性髓性白血病或骨髓增生异常综合征患者接受了治疗，在第 7 天和此后每周两次测量了 PPC。收集并评估了人口统计学数据、临床数据（包括胃肠道疾病、合并用药和治疗依从性）、热量和脂肪摄入量以及生物学数据。我们获得了 275 次 PPC 测量值，中位数为 430ng/ml。患有黏膜炎（P<0.001）、恶心（P=0.03）、腹泻（P=0.03）或呕吐（P=0.05）的患者其 PPC 明显更低。热量摄入较高的患者 PPC 更高（P=0.02），而脂肪摄入量的比例对 PPC 没有影响（P=0.84）。质子泵抑制剂的同时使用降低了 PPC（P=0.02），而他克莫司的使用增加了 PPC（P=0.03）。多变量分析显示，独立影响 PPC 的因素有他克莫司的同时使用（P<0.001）、黏膜炎的存在（P=0.01）和饮食（P=0.02）。本研究证实了泊沙康唑生物利用度的高度变异性，并显示了胃肠道疾病、饮食和合并用药对 PPC 的显著影响。然而，最佳的 PPC 仍有待确定，并与临床疗效相关联。
