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目的评价2种剂型的青蒿琥脂片在健康人体的生物等效性。方法采用单中心、随机、双周期、自身交叉的试验设计。36例健康男性志愿者单次口服试验制剂(青蒿琥脂片,每片含青蒿琥酯100mg)或参比制剂(青蒿琥酯片,每片含青蒿琥酯50 mg),血浆样品采用高效液相色谱-串联质谱法(HPLC-MS/MS)测定,计算两者的主要药物动力学参数,进行生物等效性评价。结果青蒿琥酯和双氢青蒿素的线性范围均为2~1000 ng·m L-1,最低定量浓度为2 ng·m L-1,批内及批间精密度RSD<15%;服用试验制剂和参比制剂后血浆中青蒿琥酯的Cmax分别为(321.36±148.23)、(321.3±182.34)μg·L-1;tmax分别为(0.59±0.69)、(0.77±0.65)h;t1/2分别为(0.72±1.57)、(0.35±0.24)h;AUC0~∞分别为(226.2±99.57)、(214.63±93.1)μg·h·L-1;AUC0~t分别(207.88±79.17)、(206.12±91.67)μg·h·L-1;试验制剂的相对生物利用度F0~t、F0~∞分别为(108.11±54.6)、(96.01±45.97)%;双氢青蒿素的Cmax分别为(1068.17±424)、(1118.75±545.02)μg·L-1;tmax分别为(0.9±0.43)、(1.09±0.62)h;t1/2分别为(1.47±0.48)、(1.38±0.42)h;AUC0~∞分别为(2187.26±683.78)、(2110.23±509.82)μg·h·L-1;AUC0~t分别(2179.14±683.03)、(2100.42±509.72)μg·h·L-1;试验制剂的相对生物利用度F0~t、F0~∞分别为(101.9±29.85)、(101.96±29.71)%。结论试验制剂和参比制剂具有生物等效性。
Objective To evaluate the bioequivalence of two kinds of artesunate tablets in healthy volunteers. Methods Single-center, randomized, double-cycle, crossover trial design. Thirty-six healthy male volunteers received either a single oral test formulation (artesunate tablets, each containing artesunate 100 mg) or a reference formulation (artesunate tablets containing 50 mg of artesunate per tablet), plasma Samples were analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS / MS), and the main pharmacokinetic parameters were calculated for bioequivalence. Results The linear range of artesunate and dihydroartemisinin was 2 ~ 1000 ng · m L-1 with the lowest concentration of 2 ng · m L-1. The intra-assay and inter-assay RSD were less than 15% The Cmax of artesunate in plasma was (321.36 ± 148.23) and (321.3 ± 182.34) μg · L-1, respectively, and the tmax was (0.59 ± 0.69) and (0.77 ± 0.65) h ; t1 / 2 were (0.72 ± 1.57) and (0.35 ± 0.24) h; AUC0 ~ ∞ were (226.2 ± 99.57) and (214.63 ± 93.1) μg · h · L -1, respectively; AUC0 ~ t were (207.88 ± 79.17) and (206.12 ± 91.67) μg · h · L-1, respectively. The relative bioavailability of the test preparations was F0 ~ t and F0 ~ ∞ of 108.11 ± 54.6 and 96.01 ± 45.97% (Cmax) were (1068.17 ± 424) and (1118.75 ± 545.02) μg · L-1, respectively. The tmax were (0.9 ± 0.43) and (1.09 ± 0.62) ± 0.42) h; AUC0 ~ ∞ were (2187.26 ± 683.78) and (2110.23 ± 509.82) μg · h · L -1, respectively; AUC0 ~ t were 2179.14 ± 683.03 and 2100.42 ± 509.72 μg · h · L- 1; The relative bioavailability of the test preparations, F0 ~ t and F0 ~ ∞, were (101.9 ± 29.85) and (101.96 ± 29.71)%, respectively. Conclusions The test and reference formulations are bioequivalent.