索他洛尔片在健康人体内的药动学研究  

Pharmacokinetics of sotalol tablets in healthy human beings

作　　者：闫小华[1] 周凡[1] 张宏久[1] 张毕奎[2] 许蕴[3] 马经野[3] 邓小敏[1] 张璇[1] 

机构地区：[1]深圳市康宁医院,广东深圳518020 [2]中南大学湘雅三医院,长沙410011 [3]深圳市第二人民医院,广东深圳518000

出　　处：《中南药学》2008年第3期306-309,共4页Central South Pharmacy

摘　　要：目的建立人血浆中索他洛尔的高效液相色谱测定方法,用于研究索他洛尔片在健康人体内的药动学。方法以0.01mol·L-1磷酸二氢钾溶液(磷酸调pH值为3.0)-乙腈(90∶10)为流动相,用AgilentTC-C18(4.6mm×250mm,5μm)柱,采用荧光检测,Ex=235nm,Em=313nm。结果索他洛尔线性范围为0.02～2.50μg.mL-1(r=0.9995),平均回收率为102.0%,日内RSD≤3.4%,日间RSD≤7.3%。12名受试者单次服用160mg索他洛尔片后,体内呈一室模型药动学特征。结论分析方法简单、快速、准确、灵敏度高,适用于索他洛尔的药动学及生物利用度研究。Objective To determine sotalol in human plasma by HPLC method and to study its pharmacokinetics in healthy volunteers.Methods Sotalol concentrations in the plasma were determined by HPLC-fluorescence.Perchloric acid solution（72%）was added.The solution was then mixed by vortexing and centrifuging at 9 000 r·min^-1 for 15 min（the temperature was maintained at 4 ℃）,and then was separated on an Agilent TC-C18（4.6 mm × 250 mm,5 μm）.The mobile phase consisted of 0.01 mol·L^-1 KH2PO4（pH 3.0）-acetonitrile（90∶10）;the spectrofluorometric was determined∶Ex=235 nm and Em=313 nm.Plasma concentration of sotalol was measured after taking a single dose of 160 mg in 12 subjects.The pharmacokinetic parameters were obtained with DAS 2.0.Results The calibration curve was linear within 0.02～2.50 μg·mL^-1（r=0.999 5）,the recovery was 102.0%,and the RSDs of intra-day and inter-day were ≤3.4% and ≤7.3%.After a singal oral dose of 160 mg sotalol test tablets,the main pharmacokinetics parameters were as follows：The tmax,Cmax,Ka,V/F and t1/2 were（3.3±0.9）h,（1.30±0.25）μg·mL^-1,（1.95±2.96）h-1,（119.91±20.51）L,and（10.9±1.9）h.Conclusion The method is rapid and sensitive,and suitable to investigate the pharmacokinetics and bioavailability of sotalol.

关 键 词：索他洛尔 药物浓度 药物动力学 高效液相色谱法 

分 类 号：R969.1[医药卫生—药理学] R927.2[医药卫生—药学]