盐酸二甲双胍两种缓释微丸在健康人体内药代动力学评价

Investigation on the pharmacokinetics of the two kinds of metformin hydrochloride sustained-release pellets in healthy volunteers

目的评价 pH依赖型盐酸二甲双胍缓释微丸 (T1)和非pH依赖型盐酸二甲双胍缓释微丸(T2 )在健康人体内的药代动力学和相对生物利用度。方法 18名健康志愿者随机交叉口服单剂量(10 0 0mg)盐酸二甲双胍普通片、T1和T2后 ,利用HPLC法测定血药浓度 ,并对其进行药代动力学和相对生物利用度研究。结果盐酸二甲双胍普通片、T1和T2的 ρmax分别为 (2 38± 0 4 1)、(1 6 2± 0 34)和 (0 92± 0 2 8)mg·L-1,tmax分别为 (2 72± 0 4 6 )、(5 5 6± 0 86 )和 (4 33± 0 82 )h ,AUC0→ 2 4分别为 (14 5 0± 2 83)、(14 91± 2 5 2 )和 (6 6 3± 1 96 )mg·h·L-1,tMRT分别为 (5 2 1±0 5 4 )、(8 2 6± 0 5 1)和 (6 89± 0 4 0 )h ,相对生物利用度Fr(T1) =10 3 6 % ,Fr(T2 ) =4 5 7%。结论 pH 依赖型缓释微丸有很好的缓释效果 。

Objective To investigate the pharmacokinetics and relative bioavailability of the pH-dependent (T1) and non-pH-dependent (T2) sustained-release metformin hydrochloride pellets.Methods A single oral dose of 1 000 mg of conventional metformin hydrochloride,T1 and T2 was given to 18 healthy volunteers in a random crossover design.The drug concentration in the plasma was determined by the HPLC method.The pharmacokinetic parameters and the relative bioavailability were measured.Results The pharmacokinetic parameters of the metformin hydrochloride in conventional tablets,T1 and T2 were ρ max (2.38±0.41),( 1.62±0.34) and (0.92±0.28)mg·L -1;t max (2.72±0.46),(5.56±0.86) and (4.33±0.82) h;AUC 0→24(14.50±2.83),(14.91±2.52) and (6.63±1.96) mg·h·L -1; t MRT (5.21±0.54),(8.26±0.51) and (6.89±0.40) h,respectively.Compared with commercial tablets,the relative bioavailability of T1 and T2 was103.6% and 45.7%,respectively.Conclusions An obvious characteristic of the sustained-release pellats is shown in the concentration-time curves of metformin hydrochloride in T1 in healthy volunteers.T1 and commercial tablets are bioequivalent.