University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, P.O. Box 30.001, 9700 RB Groningen, the Netherlands.
University of Groningen, University Medical Center Groningen, Department of Hematology, Groningen, the Netherlands.
Int J Antimicrob Agents. 2019 Mar;53(3):325-329. doi: 10.1016/j.ijantimicag.2019.01.006. Epub 2019 Jan 11.
During inflammation, several cytochrome P450 enzymes are downregulated. Recently it was shown that voriconazole metabolism is reduced during inflammation. Posaconazole, another triazole with broad-spectrum antifungal activity, is metabolised only to a limited extent by cytochrome P450 enzymes and to a wider extent by phase 2 enzyme systems. The aim of this study was to investigate posaconazole concentrations during inflammation. Patients aged ≥18 years receiving posaconazole prophylaxis or treatment for fungal infections were enrolled in a prospective observational study. Samples for posaconazole and C-reactive protein (CRP) concentrations were collected routinely for each patient. Longitudinal data analysis was performed to analyse the correlation between posaconazole serum trough concentrations and CRP values, corrected for potential factors that could influence the posaconazole concentration. Between August 2015 and June 2017, 64 patients were recruited to this study. Data for 55 patients (511 posaconazole samples) were included in the final analysis. The overall median posaconazole concentration was 1.8 mg/L [interquartile range (IQR) 1-2.9 mg/L, range 0.1-7.94 mg/L] and the overall median CRP concentration was 23.5 mg/L (IQR 5-75 mg/L, range 0-457 mg/L). Longitudinal data analysis showed that only the posaconazole daily dose (in mg/kg body weight) had a significant influence on posaconazole concentration after correction for other factors (P < 0.0001). Posaconazole concentrations were not influenced by CRP concentrations (P = 0.77). Posaconazole concentrations are not influenced by inflammation, reflected by CRP concentration. Therefore, more frequent therapeutic drug monitoring of posaconazole during inflammation or after an infection subsides is not necessary.
在炎症期间，几种细胞色素 P450 酶被下调。最近表明，伏立康唑代谢在炎症期间减少。泊沙康唑是另一种具有广谱抗真菌活性的三唑类药物，仅被细胞色素 P450 酶有限地代谢，而更多地被相 2 酶系统代谢。本研究旨在研究炎症期间泊沙康唑的浓度。接受泊沙康唑预防或治疗真菌感染的年龄≥18 岁的患者入组了一项前瞻性观察性研究。为每位患者常规采集泊沙康唑和 C 反应蛋白（CRP）浓度的样本。进行了纵向数据分析，以分析泊沙康唑血清谷浓度与 CRP 值之间的相关性，同时校正了可能影响泊沙康唑浓度的潜在因素。在 2015 年 8 月至 2017 年 6 月期间，这项研究共招募了 64 名患者。最终分析纳入了 55 名患者（511 个泊沙康唑样本）的数据。总体中位数泊沙康唑浓度为 1.8 mg/L [四分位距（IQR）1-2.9 mg/L，范围 0.1-7.94 mg/L]，总体中位数 CRP 浓度为 23.5 mg/L（IQR 5-75 mg/L，范围 0-457 mg/L）。纵向数据分析表明，仅泊沙康唑每日剂量（mg/kg 体重）在校正其他因素后对泊沙康唑浓度有显著影响（P < 0.0001）。CRP 浓度对泊沙康唑浓度没有影响（P=0.77）。炎症（CRP 浓度）不影响泊沙康唑浓度。因此，在炎症期间或感染消退后，不需要更频繁地监测泊沙康唑的治疗药物浓度。
