HPLC测定人血浆中伊曲康唑的浓度及生物等效性研究

Determination of Itraconazole in Human Plasma by HPLC and Studies of Bioequivalence

目的建立HPLC测定伊曲康唑人血浆中浓度和评价伊曲康唑分散片的生物等效性。方法18名健康志愿者单剂量po分散片及胶囊2种伊曲康唑制剂(各含伊曲康唑0.1g)后测定不同时间血药浓度,采用Kromail C18色谱柱(4.6mm×250mm,5μm),以乙腈-水(78∶22)为流动相,流速1.0mL·min-1;检测波长263nm,检测器灵敏度0.01AUFS,20μL定量环进样。结果受试制剂伊曲康唑分散片和参比制剂伊曲康唑胶囊中伊曲康唑的主要药动学参数:达峰时间为(3.89±0.32)和(3.94±0.24)h,达峰时药物浓度为(1601.12±151.03)和(1678.74±200.37)μg·L-1,消除相半衰期为(16.50±1.80)和(16.43±1.35)h,药-时曲线下面积AUC0-72为(21194.89±2604.04)和(21795.72±2657.52)μg·h·L-1,AUC0-∞为(22418.87±2921.60)和(23060.62±2865.28)μg·h·L-1。结论2种伊曲康唑制剂具有生物等效性。

OBJECTIVE To study the bioequivalence of itraconazole and establish a HPLC method for the determination of itraeonazole in human plasma. METHODS The randomized, crossed-over study was conducted in 18 healthy volunteers. After a single dose （containing 100 mg itcaconazole） was adminstered, the plasma drug levels were determined by HPLC. The column was Kromail C18 （4. 6 mm × 250 mm,5 μm） with acetonitrile-water（78： 22） as the mobile phase. The detection wavelength was 263 nm. The flow rate was 1.0 mL· min^-1. RESULTS The main pharmacokinetie parametes of test and reference preparation were as follows ： tmax （3.89 ± 0. 32 ） and （3.94 ± 0. 24） h, pmax, （ 1 601.12 ± 151.03 ） and （ 1 678.74 ± 200. 37 ） μg · L^-1, t1/2 （ 16. 50 ± 1.80） and （16.43 ± 1.35）h, AUC0-72 （21 194.89 ±2 604.04） and （21 795.72 ±2 657.52） μg · h · L^-1, AUC0-∞ （22418.87 ± 2 921.60） and （23 060. 62 ± 2 865.28） μg · h · L^-1. CONCLUSION The results showed that the two formulations were bioequivalent.