国产与进口富马酸比索洛尔片剂的人体生物等效性比较

Bioequivalence of domestic and imported bisoprolol tablets

目的:比较国产与进口富马酸比索洛尔片剂的生物等效性。方法:筛选20例男性健康志愿者,采用随机双交叉设计,分别给予国产以及进口富马酸比索洛尔片剂10mg,于服药前以及服药后0.5～48h间隔内定时采集血样,应用高效液相色谱-荧光检测法测定样品浓度。色谱条件为,色谱柱:KYA HiQsil(150mm×4.6mm,5μm);流动相:乙腈-水-lmol·L^(-1)磷酸二氢铵溶液(25:70:5);检测波长:Ex=226 nm,Em=300nm;流速:1.0mL·min^(-1);进样量:80μL。根据测定结果计算主要药动学参数,并以进口片剂为参比制剂,评估国产富马酸比索洛尔片剂的生物等效性。结果:本研究建立了健康人血浆中比索洛尔浓度的高效液相色谱-荧光检测法,方法的线性范围为2.5～80.0ng·mL^(-1),最低定量限为2.5ng·mL^(-1)。方法准确度在100.20%～104.26%范围内;日内、日间RSD均小于5%。20例健康志愿者口服比索洛尔受试及参比制剂后,C_(max)分别为(52.94±12.21)和(57.63±9.82)ng·mL^(-1);T_(max)分别为(1.65±0.59)和(1.55±0.54)h;t_(1/2)分别为(12.15±1.47)和(11.94±2.16)h;AUC_(0～1)分别为(680.55±138.08)和(715.18±124.22)ng·mL^(-1)·h,AUC_(0～∞)分别为(742.90±151.48)和(781.00±141.28)ng·mL^(-1)·h,口服比索洛尔受试制剂后相对生物利用度F_(0～1)和F_(0～∞)分别为(95.98±16.12)%和(95.99±15.74)%。结论:国产与进口的富马酸比索洛尔片剂生物等效。

Objective: To assess whether bisoprolol tablets locally manufactured (test) are bioequivalent to bisoprolol tablets imported (reference). Methods: 20 healthy male volunteers were randomly administered either a single crossover dose 10mg of both bisoprolol tablets. The blood samples from the volunteers were collected before and in 0.5～48h after dosing to measure plasma drug concentrations by HPLC-fluorescence spectrometer. The HPLC condition was as follows:a KYA HiQsil column (150mm×4.6mm,5μm), an eluant composed of acetonitrile-water-1mol·L^(-1) ammonium dihydrogen phosphate (25:70:5) with the flow rate of 1.0mL·min^(-1), and the detection at Ex=226nm and Em=300nm, respectively. Results: A linear curve of bisoprolol was in the range of 2.5～80.0ng·mL^(-1) and a detection limit was at 2.5ng·mL^(-1). The average recovery was within 100.20%～104.26% with within-day and among-days RSD of less than 5%. The pharmacokinetics parameters of test and reference tablets were shown as C_(max)(52.94±12.21) vs. (57.63±9.82) ng·mL^(-1), T_(max)(1.65± 0.59)vs.(1.55±0.54)h,t(1/2)(12.15±1.47) vs. (11.94±2.16) h,AUC_(0～t)(680.55±138.08) vs. (715.18±124.22)ng·mL^(-1)·h and AUC_(0～∞) (742.90±151.48)vs. (781.00± 141.28)ng·mL^(-1)·h. The relative bioavailability of test tablets was F_(0～t)(95.98±16.12)% and F_(0～∞) (95.99±15.74)%. Conclusion:The test tablets are bioequivalent to the reference tablets.