【摘要】 目的 建立人血浆中二甲双胍浓度的RP-HPLC测定方法,研究二甲双胍在人体中药物动力学行为,评价其生物等效性。方法 采用双交叉实验设计和单剂量、多剂量2种给药方案,测定了20名健康受试者口服盐酸二甲双胍普通片和缓释片后不同时间后的血药浓度。结果 受试者单剂量口服普通片和缓释制剂后估算的药动学参数AUC0-τ分别为(9.41±1.21)mg·h·L-1和(10.79±1.50)mg·h·L-1;t1/2分别为(2.94±0.57)h,(4.55±0.82)h,tmax分别为(1.5±0.7)h和(3.1±0.6)h;Cmax分别为(2.28±0.44)mg·L-1和(1.72±0.54)mg·L-1;MRT分别为(4.12±0.87)h和(7.32±1.45)h,相对生物利用度F为114.9％±10.7％。受试者多剂量口服普通片和缓释制剂后估算的药物动力学参数AUCss分别为(10.64±1.35)mg·h·L-1、(17.97±2.22)mg·h·L-1,Cmax分别为(2.33±0.43)mg·L-1、 (1.98±0.30)mg·L-1,Cmin分别为(0.18×0.04)mg·L-1、 (0.10±0.03)mg·L-1,Cav分别为(0.89±0.11)mg·L-1、(0.75±0.09)mg·L-1,tmax分别为(1.9±0.6)h、(2.9±0.9)h,相对生物利用度F为为85.0％±8.8％。结论 盐酸二甲双胍普通片和缓释片口服时吸收程度等效,吸收速度不等效。更多还原

【Abstract】 OBJECTIVE To focus on the pharmacokinetics and relative bioavailability of metformin hydrochloride in healthy volunteers. METHODS A single oral dose of 500 mg and a multiple oral dose of 1 000 mg of two different forms (sustained-release and general tablets) of metformin hydrochloride were given to 20 healthy male volunteers in a randomized crossover study. Drug concentrations in the plasma were measured by the reverse HPLC method. RESULTS The single oral dose pharmacokinetic parameters of general tablets and sustained-release tablets were: AUC0-τ (9. 41 ± 1.21) mg· h· L-1, (10. 79 ± 1. 50) mg ·h · L -1,t1/2: (2. 94 ± 0. 57) h, (4. 55 ± 0. 82) h; tmax: (1.5±0. 7) h, (3.1±0.6) h; Cmax (2.28 ± 0.44) mg · L-1 , (1.72 ± 0.54) mg · L-1; MRT: (4.12± 0.87) h, (7.32±1.45) h, respectively. The relative bioavailability of sustained-release tablets to general tablets was 114. 9% ±10. 7%. The multiple oral doses pharmacokinetic parameters of general tablets and sustained-release tablets were: AUCss: (10.64 ± 1.35) mg · h· L-1 , (17.97± 2.22) mg · h · L-1 , Cmax: (2.33 ± 0.43) mg · L-1 , (1.98± 0.30) mg·L-1; Cmin (0.18 ± 0.04) mg · L-1 , (0.10±0.03) mg · L-1 , Cav (0.89 ± 0.11) mg · L ’, (0.75 ± 0.09) mg · L-1 ; tmax(1.9 ± 0.6) h, (2.9± 0.9) h respectively. The relative bioavailability of capsules to tablets was 85. 0% ± 8. 8%. The pharmacokinetic parameters showed no significant differences between the two different forms (P>0. 05). CONCLUSIONS The two different forms of metformin hydrochloride are bioequiva-lent.更多还原