国产复方缬沙坦片人体相对生物利用度研究

Study on Relative Bioavailability of Domestic Compound Valsartan Tablets in Human Body

目的评价国产复方缬沙坦片在健康人体的相对生物利用度,并与参比制剂比较其生物等效性。方法将18名男性健康志愿者随机分组,依照自身交叉、对照方案单剂量口服国产复方缬沙坦片及参比制剂各2片(含缬沙坦160mg/氢氯噻嗪25mg),采用高效液相色谱(HPLC)-荧光法及离子对色谱法测定血浆中缬沙坦、氢氯噻嗪的质量浓度,并用BAPP2.0软件计算药代动力学参数。结果国产复方缬沙坦片和参比制剂的主要药代动力学参数,缬沙坦达峰时间(Tmax)分别为(2.75±0.55)h和(2.75±0.31)h,峰浓度(Cmax)分别为(4496.44±1453.66)ng/mL和(4387.46±1445.47)ng/mL,0～24h药时曲线下面积AUC0-24分别为(28955.11±8122.35)ng/(h.mL)和(29783.15±9706.08)ng/(h.mL);氢氯噻嗪Tmax分别为(2.44±0.66)h和(2.25±0.35)h,Cmax分别为(136.68±33.91)ng/mL和(128.12±37.35)ng/mL,AUC0-24分别为(1018.54±200.73)ng/(h.mL)和(1008.44±292.30)ng/(h.mL)。国产复方缬沙坦片中的缬沙坦和氢氯噻嗪的相对生物利用度(F)分别为(99.8±15.5)%和(107.9±30.6)%。结论受试制剂与参比制剂具有生物等效性。

Objective To evaluate the relative bioavailability of domestic Compound Valsartan Tablets in healthy human body and to compare the bioequivalence with reference tablets. Methods 18 healthy male volunteers were randomly divided into the groups,ac- cording to the self crossover controlled scheme, and orally took a single dose of domestic Compound Valsartan Tablets and the 2 refer- ence tablets which contain valsartan 160 mg/hydrochlorothiazide 25 mg respectively. The HPLC- fluorescence method and the iron- pair chromatographic method were adopted to determine the plasma concentrations of valsartan and hydrochlorothiazide. The pharmacokinetic parameters were calculated by BAPP2.0 software. Results The main pharmacokinetic parameters of domestic Compound Valsartan Tablets and the reference preparation were as follows. Valsartan： Tmax was （2.75-＋0. 55）h and （2.75 ＋0. 31）h, Cax was （4 496.44 ＋ 1 453.66）ng/mL and （4 387.46＋1 445.47）ng/mL,AUC^o-24~ was （28 955.11_＋8 122.35） ng/（h mL） and （29 783.15_＋ 9 706. 08 ） ng/（h ~ mL）. Hydrochlorothiazide ： T^x was （2.44 _＋ 0. 66 ） h and （2. 25 _＋ 0. 35 ） h, Cm= was （ 136. 68 _＋ 33.91 ） ng/mL and （128. 12 ＋37.35） ng/mL, AUCa- 24was （901.36 ＋ 164. 19） ng/（h mL） and （890. 92-＋265.75） ng/（h ~ mL） .The relative bioavailabilities（F） of valsartan and hydrochlorothiazide in domestic Compound Valsartan Tablets were （99.8 ＋ 15.5）% and （103.9 ＋ 30. 6）% respectively. Conclusion The test preparation and the reference preparation have bioequivalence.