三氟柳胶囊单剂量与多剂量人体药动学研究

发布时间：2018-08-03 07:15

【摘要】：目的:研究三氟柳胶囊在健康人体内的药动学特征。方法:采用单中心随机试验设计,将36名健康受试者分为3组,分别单剂量口服三氟柳胶囊低、中、高剂量(300、600、900 mg),qd,给药当天进行单剂量人体药动学研究;中剂量组继续给药13 d,进行多剂量人体药动学研究。采用液相色谱-串联质谱(LC-MS/MS)法测定三氟柳血药浓度,色谱柱为Zorbax SB-C18,流动相为甲醇-0.2%甲酸水溶液(80∶20,V/V),流速为0.2 ml/min;采用电喷雾离子源(ESI),以多反应监测(MRM)模式扫描,负离子方式检测,用于定量分析的离子对分别为m/z 247.1→161.1(三氟柳)、m/z 294.0→250.0(内标,双氯芬酸钠)。采用Win Nonlin 6.2软件计算药动学参数,并比较其差异。结果:三氟柳血药浓度在0.05~20.0μg/ml范围内线性关系良好。单剂量低、中、高剂量组t1/2分别为(0.45±0.20)、(0.47±0.10)、(0.43±0.20)h,tmax分别为(0.56±0.20)、(0.60±0.20)、(0.47±0.40)h,c_(max)分别为(3.30±0.98)、(10.65±3.26)、(13.96±4.88)μg/ml,AUC_(0-8 h)分别为(3.99±0.93)、(13.29±1.72)、(19.62±6.78)μg·h/ml,300~900 mg剂量范围内,c_(max)、AUC_(0-8 h)与剂量呈线性关系(R2分别为0.954、0.986)。多剂量给药达稳态时,平均血药浓度为(0.71±0.20)μg/ml,AUCss为(17.10±4.82)μg·h/ml,t1/2为(0.49±0.10)h,tmax为(0.85±0.62)h,c_(max)为(11.58±3.99)μg/ml,AUC_(0-8 h)为(16.99±4.84)μg·h/ml,AUC0-∞为(17.08±4.81)μg·h/ml,蓄积因子为(1.28±0.40)。单剂量给药与多剂量给药的tmax和t1/2相近。结论:LC-MS/MS法能快速、准确地测定三氟柳在人体血浆中的浓度。三氟柳胶囊在健康受试者体内存在蓄积现象,且具线性药动学特征。
[Abstract]:Objective: to study the pharmacokinetics of Sanfluru capsule in healthy volunteers. Methods: Thirty-six healthy subjects were divided into three groups by a single-center randomized trial design. The pharmacokinetics of single dose of Sanfluru capsule was studied on the same day with low, medium and high doses (300600900 mg / d). In medium dose group, the pharmacokinetics of multi-dose human was studied for 13 d. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to determine the concentration of triflurane in blood. The chromatographic column was Zorbax SB-C18, the mobile phase was methanol-0.2% formic acid solution (80: 20 V / V), the flow rate was 0.2 ml / min, and the electrospray ion source (ESI),) was used to monitor (MRM) mode. The ion pairs used for quantitative analysis were m / z 247.1 ~ (161.1) m / r / z 294.0 ~ 250.0 (internal standard, diclofenac sodium). The pharmacokinetic parameters were calculated by Win Nonlin 6. 2 software and the differences were compared. Results: the serum concentration of triflurane showed a good linear relationship in the range of 0.05 ~ 20.0 渭 g/ml. 鍗曞墏閲忎綆,涓，

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