多剂量口服盐酸氨溴索缓释胶囊的人体药代动力学及相对生物利用度

Multiple dose pharmacokinetics and relative bioavailability of ambroxol hydrochloride sustained release capsules in healthy volunteers

目的 研究多剂量口服盐酸氨溴索缓释胶囊的人体药代动力学和相对生物利用度。方法 选择盐酸奎宁为定量内标物 ,采用反相高效液相色谱法测定了多剂量口服 75mg盐酸氨溴索国产缓释胶囊和进口缓释胶囊在健康人体内的盐酸氨溴索血药浓度 ,以考察盐酸氨溴索缓释胶囊多剂量口服达稳态过程和稳态药代动力学特征。结果 75mg盐酸氨溴索缓释胶囊连续口服d 4起 ,体内盐酸氨溴索血药浓度基本达稳态水平。国产缓释胶囊和进口缓释胶囊的稳态药代动力学参数Tmax分别为 (4 2± 0 7)h和 (4 1± 0 8)h ,Cmax分别为 (2 0 8 73± 31 91) μg·L-1和 (2 12 5 6± 2 9 6 4) μg·L-1,Cmin分别为 30 76± 10 47μg·L-1和 (2 9 80± 10 2 3)μg·L-1,AUCss分别为 (2 113 90± 430 6 0 ) μg·h·L-1和2 0 88 2 2± 40 2 5 2 μg·h·L-1,Cav分别为 (88 0 8± 17 94) μg·L-1和 (87 0 1± 16 77) μg·L-1,DF分别为 (2 0 7± 0 31)和(2 16± 0 37) ,多剂量口服 75mg国产盐酸氨溴索缓释胶囊的相对生物利用度为 10 1 10 %± 6 33 %。结论 盐酸氨溴索国产缓释胶囊和进口缓释胶囊的主要稳态药代动力学参数差异均无显著性 。

AIM\ To study the multiple dose pharmacokinetics and relative bioavailability of ambroxol hydrochloride sustained release capsules in 12 male healthy volunteers. METHODS\ A reversed phase high performance liquid chromatography (RP HPLC) with quinine dihydrochloride as the internal standard was established for the determination of ambroxol hydrochloride in plasma after multiple administration of a daily dose of 75 mg ambroxol hydrochloride domestic and imported sustained release capsules in a randomized crossover design.The fluctuation of ambroxol hydrochloride valley concentrations was observed and the steady state pharmacokinetics was characterized in a multiple dose schedule of 75 mg ambroxol hydrochloride sustained release capsules. RESULTS\ The steady state of ambroxol hydrochloride plasma concentrations was reached at the fourth oral administration of 75 mg ambroxol hydrochloride sustained release capsules. The steady state pharmacokinetic parameters after multiple oral dose of 75 mg ambroxol hydrochloride domestic and imported sustained release capsules were as follows: T max were (4 2±0 7) h and (4 1±0 8) h, C max were (208 73±31 91)μg·L -1 and (212 56±29 64) μg·L -1 , C min were (30 76±10 47)μg·L -1 and (29 80±10 23)μg·L -1 , AUC ss were (2113 90±430 60)μg·h -1 ·L -1 and 2088 22±402 52 μg·h·L -1 , C av were (88 08±17 94)μg·L -1 and (87 01±16 77)μg·L -1 , DF were (2 07±0 31) and (2 16±0 37), respectively. The relative bioavailability of multiple oral dose of 75 mg domestic ambroxol hydrochloride sustained release capsules was 101 10%±6 33%. CONCLUSION\ There were no significant differences in the main steady state pharmacokinetic parameters between domestic, and imported sustained release capsules and the two capsules were bioequivalent.