【摘要】：目的:研究三氟柳膠囊在健康人體內(nèi)的藥動(dòng)學(xué)特征。方法:采用單中心隨機(jī)試驗(yàn)設(shè)計(jì),將36名健康受試者分為3組,分別單劑量口服三氟柳膠囊低、中、高劑量(300、600、900 mg),qd,給藥當(dāng)天進(jìn)行單劑量人體藥動(dòng)學(xué)研究;中劑量組繼續(xù)給藥13 d,進(jìn)行多劑量人體藥動(dòng)學(xué)研究。采用液相色譜-串聯(lián)質(zhì)譜(LC-MS/MS)法測(cè)定三氟柳血藥濃度,色譜柱為Zorbax SB-C18,流動(dòng)相為甲醇-0.2%甲酸水溶液(80∶20,V/V),流速為0.2 ml/min;采用電噴霧離子源(ESI),以多反應(yīng)監(jiān)測(cè)(MRM)模式掃描,負(fù)離子方式檢測(cè),用于定量分析的離子對(duì)分別為m/z 247.1→161.1(三氟柳)、m/z 294.0→250.0(內(nèi)標(biāo),雙氯芬酸鈉)。采用Win Nonlin 6.2軟件計(jì)算藥動(dòng)學(xué)參數(shù),并比較其差異。結(jié)果:三氟柳血藥濃度在0.05~20.0μg/ml范圍內(nèi)線性關(guān)系良好。單劑量低、中、高劑量組t1/2分別為(0.45±0.20)、(0.47±0.10)、(0.43±0.20)h,tmax分別為(0.56±0.20)、(0.60±0.20)、(0.47±0.40)h,c_(max)分別為(3.30±0.98)、(10.65±3.26)、(13.96±4.88)μg/ml,AUC_(0-8 h)分別為(3.99±0.93)、(13.29±1.72)、(19.62±6.78)μg·h/ml,300~900 mg劑量范圍內(nèi),c_(max)、AUC_(0-8 h)與劑量呈線性關(guān)系(R2分別為0.954、0.986)。多劑量給藥達(dá)穩(wěn)態(tài)時(shí),平均血藥濃度為(0.71±0.20)μg/ml,AUCss為(17.10±4.82)μg·h/ml,t1/2為(0.49±0.10)h,tmax為(0.85±0.62)h,c_(max)為(11.58±3.99)μg/ml,AUC_(0-8 h)為(16.99±4.84)μg·h/ml,AUC0-∞為(17.08±4.81)μg·h/ml,蓄積因子為(1.28±0.40)。單劑量給藥與多劑量給藥的tmax和t1/2相近。結(jié)論:LC-MS/MS法能快速、準(zhǔn)確地測(cè)定三氟柳在人體血漿中的濃度。三氟柳膠囊在健康受試者體內(nèi)存在蓄積現(xiàn)象,且具線性藥動(dòng)學(xué)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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