University of Groningen, University Medical Center Groningen, Department of Hospital and Clinical Pharmacy, Groningen, the Netherlands.
Antimicrob Agents Chemother. 2013 Oct;57(10):4999-5004. doi: 10.1128/AAC.00707-13. Epub 2013 Jul 29.
Invasive aspergillosis and candidemia are important causes of morbidity and mortality in immunocompromised and critically ill patients. The triazoles voriconazole, fluconazole, and posaconazole are widely used for the treatment and prophylaxis of these fungal infections. Due to the variability of the pharmacokinetics of the triazoles among and within individual patients, therapeutic drug monitoring is important for optimizing the efficacy and safety of antifungal treatment. A dried blood spot (DBS) analysis was developed and was clinically validated for voriconazole, fluconazole, and posaconazole in 28 patients. Furthermore, a questionnaire was administered to evaluate the patients' opinions of the sampling method. The DBS analytical method showed linearity over the concentration range measured for all triazoles. Results for accuracy and precision were within accepted ranges; samples were stable at room temperature for at least 12 days; and different hematocrit values and blood spot volumes had no significant influence. The ratio of the drug concentration in DBS samples to that in plasma was 1.0 for voriconazole and fluconazole and 0.9 for posaconazole. Sixty percent of the patients preferred DBS analysis as a sampling method; 15% preferred venous blood sampling; and 25% had no preferred method. There was significantly less perception of pain with the DBS sampling method (P = 0.021). In conclusion, DBS analysis is a reliable alternative to venous blood sampling and can be used for therapeutic drug monitoring of voriconazole, fluconazole, and posaconazole. Patients were satisfied with DBS sampling and had less pain than with venous sampling. Most patients preferred DBS sampling to venous blood sampling.
侵袭性曲霉病和念珠菌血症是免疫功能低下和重症患者发病率和死亡率的重要原因。三唑类药物伏立康唑、氟康唑和泊沙康唑广泛用于这些真菌感染的治疗和预防。由于三唑类药物在个体患者之间和个体内部的药代动力学存在差异，因此治疗药物监测对于优化抗真菌治疗的疗效和安全性非常重要。我们开发了一种干血斑 (DBS) 分析方法，并在 28 名患者中对伏立康唑、氟康唑和泊沙康唑进行了临床验证。此外，还进行了问卷调查以评估患者对采样方法的意见。DBS 分析方法显示所有三唑类药物的浓度范围内均具有线性。准确度和精密度的结果均在可接受范围内；样本在室温下至少稳定 12 天；并且不同的红细胞压积值和血斑体积没有显着影响。DBS 样本中药物浓度与血浆中药物浓度的比值为伏立康唑和氟康唑的 1.0，泊沙康唑的 0.9。60%的患者更喜欢 DBS 分析作为采样方法；15%的患者更喜欢静脉血采样；25%的患者没有首选方法。DBS 采样方法的疼痛感明显较轻（P = 0.021）。总之，DBS 分析是静脉血采样的可靠替代方法，可用于伏立康唑、氟康唑和泊沙康唑的治疗药物监测。患者对 DBS 采样满意，且疼痛感比静脉采样轻。大多数患者更喜欢 DBS 采样而不是静脉血采样。
