Taghvaye-Masoumi Hamidreza, Hadjibabaie Molouk, Ghadimi Maryam, Zarif-Yeganeh Morvarid, Vaezi Mohammad, Ghavamzadeh Ardeshir
Department of Clinical Pharmacy, Faculty of Pharmacy, Guilan University of Medical Sciences, Rasht, Iran.
Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2021 Winter;20(1):62-71. doi: 10.22037/ijpr.2020.112330.13688.
There are conflicting data regarding the association between plasma concentration of voriconazole (VCZ) and both efficacy and safety. This study investigates the association of VCZ trough plasma level with clinical efficacy and hepatotoxicity in the Iranian population suffering hematological malignancies. This cross-sectional study was performed on adult Iranian patients (age ≥ 18 years) with hematological malignancies undergoing treatment with oral or intravenous VCZ for proven or probable invasive Plasma concentrations of VCZ were measured at two time points on day 4 and 14 during the study period. A total of 60 VCZ trough concentrations of 30 patients were drawn on days 4 and 14 after the initiation of treatment. There was no definite correlation between the mean plasma concentration of VCZ and VCZ dosage ( 0.134, r = 0.280). In multivariable model, only plasma concentration of VCZ on day 14 was associated with the incidence of hepatotoxicity ( 0.013; OR = 1.42, 95% CI = 1.07-3.24). Plasma trough concentration neither on day 4 nor on day 14 was related to the treatment response. No significant association was observed between the mean plasma concentration of VCZ and 3-month patients' survival ( 0.696). To conclude, VCZ trough concentration may not be a predictor of treatment response or 3-month patients' survival. However, the wide inter- and intra-patient variability of VCZ plasma concentration coupled with the observed association between VCZ trough level and the incidence of hepatotoxicity would pose the question regarding the potential benefit of VCZ concentration monitoring.
关于伏立康唑(VCZ)血浆浓度与疗效及安全性之间的关联,存在相互矛盾的数据。本研究调查了伊朗血液系统恶性肿瘤患者中VCZ血浆谷浓度与临床疗效及肝毒性之间的关联。这项横断面研究针对的是成年伊朗患者(年龄≥18岁),他们患有血液系统恶性肿瘤,正在接受口服或静脉注射VCZ治疗以确诊或疑似侵袭性感染。在研究期间的第4天和第14天两个时间点测量了VCZ的血浆浓度。在治疗开始后的第4天和第14天,共采集了30例患者的60个VCZ谷浓度样本。VCZ的平均血浆浓度与VCZ剂量之间没有明确的相关性(P = 0.134,r = 0.280)。在多变量模型中,仅第14天的VCZ血浆浓度与肝毒性发生率相关(P = 0.013;OR = 1.42,95%CI = 1.07 - 3.24)。第4天和第14天的血浆谷浓度均与治疗反应无关。未观察到VCZ的平均血浆浓度与患者3个月生存率之间存在显著关联(P = 0.696)。总之,VCZ谷浓度可能不是治疗反应或患者3个月生存率的预测指标。然而,VCZ血浆浓度在患者间和患者内的广泛变异性,以及观察到的VCZ谷浓度与肝毒性发生率之间的关联,引发了关于监测VCZ浓度潜在益处的问题。