Hassan Metwally M A, Jansen J A, Overgaard J
Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
Clin Oncol (R Coll Radiol). 2015 Mar;27(3):168-75. doi: 10.1016/j.clon.2014.11.024. Epub 2014 Dec 16.
To study the pharmacokinetic characteristics of the hypoxic radiosensitiser nimorazole in patients with head and neck squamous cell carcinoma.
The pharmacokinetics of the hypoxic radiosensitiser nimorazole were studied in 63 patients treated in the DAHANCA-5 trial. After the first day of treatment, serial venous blood samples were taken and plasma concentrations of nimorazole measured by high pressure liquid chromatography (HPLC). Plasma concentration profiles were subjected to non-compartmental pharmacokinetic analysis using validated PC-based software. The different pharmacokinetic parameters were calculated and correlated with the different patient- and treatment-related variables.
HPLC measurements showed a linear relationship between peak plasma concentration and administered dose. The mean peak concentration adjusted for dose (in g/m(2)) was 32.2 ± 0.9 μg/ml. The time of peak concentration ranged between 30 and 180 min (median 60 min). Plasma elimination occurred with a mean half-life of 3.35 ± 0.09 h and was not significantly altered as a function of dose. There was a well-established linear-linear relationship between area under the concentration-time curve (AUC; mean 191 ± 6 μg·h/ml) and administered dose, especially when expressed as g/m(2). The mean apparent volume of distribution was 0.77 ± 0.02 l/kg. A statistically significant longer elimination half-life in men relative to women (mean difference 0.40 h; 95% confidence interval 0.77-0.03; P 0.03) was detected. Nimorazole was well tolerated; with 67% of patients reporting no toxicity; nausea/vomiting was the most reported toxicity in the remaining patients.
The study supports the current nimorazole dose scheduling in patients.
研究缺氧放射增敏剂尼莫唑在头颈部鳞状细胞癌患者中的药代动力学特征。
在DAHANCA - 5试验中，对63例接受治疗的患者进行了缺氧放射增敏剂尼莫唑的药代动力学研究。治疗首日之后，采集系列静脉血样，采用高压液相色谱法（HPLC）测定血浆中尼莫唑的浓度。使用经过验证的基于个人电脑的软件，对血浆浓度曲线进行非房室药代动力学分析。计算不同的药代动力学参数，并将其与不同的患者及治疗相关变量进行关联分析。
HPLC测量结果显示，血浆峰浓度与给药剂量之间呈线性关系。调整剂量（以g/m²计）后的平均峰浓度为32.2±0.9μg/ml。峰浓度出现时间在30至180分钟之间（中位数为60分钟）。血浆消除的平均半衰期为3.35±0.09小时，且未随剂量变化而显著改变。浓度 - 时间曲线下面积（AUC；平均值为191±6μg·h/ml）与给药剂量之间存在良好确立的线性 - 线性关系，尤其是以g/m²表示时。平均表观分布容积为0.77±0.02l/kg。检测到男性的消除半衰期相对于女性在统计学上显著更长（平均差异为0.40小时；95%置信区间为0.77 - 0.03；P = 0.03）。尼莫唑耐受性良好；67%的患者报告无毒性；其余患者中，恶心/呕吐是最常报告的毒性反应。
该研究支持目前对患者使用的尼莫唑剂量方案。
