复方厄贝沙坦分散片在健康志愿者体内的生物等效性

Bioequivalence study of compound irbesartan dispersible tablets

目的建立测定人血浆样品中厄贝沙坦浓度的HPLC-UV方法,并研究复方厄贝沙坦分散片的人体生物等效性。方法20名男性健康受试者交叉口服单剂量受试制剂或参比制剂后,不同时间点采血,以氯雷他定为内标,血浆样品经乙腈沉淀蛋白,应用HPLC-UV法测定血药浓度经时过程,计算相关药动学参数,评价两制剂的生物等效性。结果单剂量口服受试制剂与参比制剂后厄贝沙坦的相关药动学参数tmax分别为(1.8±0.7)和(1.7±0.6)h;ρmax分别为(1204.6±240.5)和(1251.7±295.3)μg.L-1;t12分别为(5.8±4.6)和(6.6±7.3)h;AUC0→t分别为(9053.1±4131.5)和(9851.8±4336.9)μg.h.L-1;AUC0→∞分别为(10524.4±5263.2)和(11606.8±5842.1)μg.h.L-1。以AUC0→t计算,受试制剂的相对生物利用度平均为(94.2±21.3)%。结论本方法可靠、准确性高、操作快速、简便。受试制剂与参比制剂生物等效。

AIM To develop a simple, selective RP-HPLC method for the determination of irbesartan concentration in human plasma. With the method, the pharmacokineties and bioequivalence of compound irbesartan dispersible tablets were studied. METHODS The human plasma samples were collected at predetemined time points after giving the 20 healthy volunteers a single oral dose of test drug or reference one. Loratadine was selected as the internal standard, and acetonitrile was selected to precipitate protein. The plasma samples were determined by HPLC-UV method. The relative pharmaeokinetic parameters were calculated to evaluate the bioequivalence of compound irbesartan dispersible tablets. RESULTS The relative pharmacokinetic parameters of irbesartan in test and reference formulations were as follows： tmax （1.8±0.7） and （1.7±0.6）h;ρmax（1 204.6±240.5） and （1 251.7 ±295.3）μg·L^-1; t1/2（5.8 ±4.6） and （6.6± 7.3） h; AUC0→t （9 053.1 ± 4 131.5 ） and （9 851.8 ± 4 336.9）μg·h·L^-1 ; AUC0→∞（ 10 524.4 ± 5 263.2） and （11 606.8 ± 5 842.1 ） μg·h·L^-1. The relative bioavailability of compound irbesartan dispersible tablets was （94.2 ± 21.3）%. CONCLUSION The established HPLC method is accurate,rapid and reliable. The statistical analysis results show that the two formulations are bioequivalent.