反相高效液相色谱法测定茚地那韦2种制剂在健康人体的相对生物利用度(英文)  

Relative bioavailability of two formulations of indinavir in Chinese healthy volunteers by reversed phase high performance liquid chromatography

作　　者：乔海灵[1] 郜娜[1] 郭玉忠[1] 张莉蓉[1] 张启堂[1] 贾琳静[1] 

机构地区：[1]郑州大学临床药理研究所,河南郑州450052

出　　处：《中国新药与临床杂志》2005年第11期841-844,共4页Chinese Journal of New Drugs and Clinical Remedies

摘　　要：目的：建立高效液相色谱法测定血浆中茚地那韦2种制剂的浓度，并比较相对生物利用度。方法：采用反相高效液相色谱法测定18名男性健康受试者单剂量交叉口服800mg两种茚地那韦胶囊后不同时间血浆中的药物浓度。萃取溶剂为乙腈。色谱条件：Hypersil ODS C18，流动相为乙腈：0．01mol·L^-1磷酸盐缓冲液（pH5．5）=43：57。检测波长为210nm。线性范围为0．03～16．38mg·L^-1。结果：两者药-时曲线均符合一房室模型。试验制剂和参比制剂的药动学参数如下：cmax分别为（10．6±s2．4）mg·L^-1和（9．8±2．2）mg·L^-1；tmax分别为（0．71±0．19）h和（0．8±0．3）h；t1/2ke分别为（1．30±0．24）h和（1．31±0．23）h；AUC0-10分别为（23±6）mg·h·L^-1。和（22±5）nag·h·L^-1；AUC0-∞。分别为（24±6）nag·h·L^-1和（22±5）mg·h·L^-1。双向单侧t检验证明。两制剂的主要药动学参数无明显差异。结论：所建立的HPLC法适用于测定人血浆中茚地那韦的浓度，试验制剂与参比制剂具有生物等效性。AIM： To establish a method to determine the concentration of indinavir in human plasma and study indinavir bioavailability in Chinese healthy people. METHODS： In a random two-period crossover study, 18 healthy male volunteers received a single dose of indinavir capsules 800 mg of two formulations respectively. A sensitive and specific reversed phase HPLC method was developed to quantitate plasma levels of indinavir. The drug was extracted from plasma with aeetonitrile. Analysis was performed on a Hypersil C18 column with a mobile phase of acetonitrile： 0.01 mol · L^-1 phosphate buffer（pH 5.5） （43： 57）. The UV detector was set at 210 nm. The standard curve covered the concentration ranged from 0. 03 to 16.38 mg · L^-1. RESULTS： The concentration-time curves of reference and tested formulations both fitted to a one-compartment open model. The main pharmacokinetic parameters of tested and reference formulations were （10.6 ±s 2.4） mg · L^-1 and （9.8 ±2.2） mg · L^-1 for Cmax （0. 71 ± 0. 19） h and （0. 8 ± 0.3） h for tin=, （1.30±0.24） h and （1.31 ±0.23） h for t1/2ke, （23 ±6） mg ·h· L^-1 and （22 ±5） mg ·h· L^-1 for AUC0-10, （24±6） mg·h· L^-1 and （22 ± 5） mg ·h· L^-1 for AUC0-10 , respectively. Two one-side t test and variance analysis were performed in bioequivalent assessment. No statistically significant difference was found in AUC0-10, AUC0-10 and cmax values between the tested and reference formulations. CONCLUSION： The reversed phase HPLC is a reliable method to determine the concentration of indinavir in human plasma and the two formulations of indinavir are bioequivalent.

关 键 词：茚地那韦 色谱法 高压液相 药动学 生物等效性 

分 类 号：R969.1[医药卫生—药理学] R978.7[医药卫生—药学]