Transpl Infect Dis:免疫功能低下者,糖皮质激素使用对伏立康唑血药浓度影响几何?

2018-09-05 王淳 环球医学

伏立康唑(VRCZ)是一种三代的三唑类抗生素,具有广谱的抗菌活性。由于非线性的药代动力学特性,VRCZ的血药浓度高度多变;此外,还受药物相互作用、肠道吸收特性、基因多态性、炎症状态、年龄和体重等多重因素的影响。2018年8月,发表在《Transpl Infect Dis》的一项研究调查了免疫功能低下患者中,糖皮质激素使用对VRCZ血药浓度的影响。

伏立康唑(VRCZ)是一种三代的三唑类抗生素,具有广谱的抗菌活性。由于非线性的药代动力学特性,VRCZ的血药浓度高度多变;此外,还受药物相互作用、肠道吸收特性、基因多态性、炎症状态、年龄和体重等多重因素的影响。2018年8月,发表在《Transpl Infect Dis》的一项研究调查了免疫功能低下患者中,糖皮质激素使用对VRCZ血药浓度的影响。

背景:VRCZ是一种广谱抗真菌药,可通过口服和静脉给药。据报道,血药治疗浓度存在高度的个体内和个体间差异。研究人员通过评估糖皮质激素剂量和VRCZ谷水平之间的相关性,分析糖皮质激素使用对VRCZ血药浓度的影响。

方法:对2010年6月至2017年3月(6年8个月)间,我院使用VRCZ联合或未联合糖皮质激素治疗的免疫功能低下患者进行评估。VRCZ和糖皮质激素通过口服或静脉给药。糖皮质激素治疗仅在VRCZ开始前或开始后3日内给药才被认为是“同时”治疗。根据抗炎作用(相对于糖皮质激素活性),所有糖皮质激素被转换为基于泼尼松龙的剂量。在稳定期的谷点检测VRCZ浓度。

结果:从38名患者获得85份样本。23名女性和15名男性的医疗记录被评估,中位年龄为61岁(范围:35-86)。21名患者(55.3%,21/38)接受化疗,28名(73.7%,28/38)接受糖皮质激素疗法。糖皮质激素的平均和中位日剂量分别是59.2和89.8 mg(范围:0.714-377)。VRCZ浓度与糖皮质激素剂量呈负相关(r=-0.26)。同未使用者相比,糖皮质激素使用者的VRCZ浓度明显降低(P=0.013)。 在研究队列中每日可获得5个点以上数据的3名患者中,研究人员评估VRCZ浓度和糖皮质激素剂量之间的相关性。个体间分析显示,VRCZ浓度的谷水平随糖皮质激素剂量的增加而降低。患者的基础疾病是血液病(n=25)和免疫性疾病(n=13)。在获益患者中,没有患者经历造血干细胞移植,并且没有患者使用已知的混淆药治疗,例如钙调磷酸酶抑制剂或苯妥英。

结论:VRCZ可被糖皮质激素诱导的酶代谢;因此,在同时治疗前,应考虑VRCZ代谢的个体内差异,尤其是对于使用糖皮质激素治疗的血液学恶性肿瘤患者。

原始出处:

Imataki O, Yamaguchi K, Uemura M, et.al. Voriconazole concentration is inversely correlated with corticosteroid usage in immunocompromised patients. Transpl Infect Dis. 2018 Aug;20(4):e12886. doi: 10.1111/tid.12886. Epub 2018 Apr 10.

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    2019-06-13 bsmagic9140
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