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目的:研究对乙酰氨基酚/酒石酸双氢可待因片在健康志愿者中的生物利用度和生物等效性。方法:22例健康志愿者随机单盲、单剂量、双周期两制剂交叉口服国产制剂(试验制剂)与进口制剂(参比制剂),剂量为酒石酸双氢可待因20 mg,对乙酰氨基酚1000 mg,用高效液相色谱法测定10个时间点的血药浓度,采用3P97程序计算主要药代动力学参数和相对生物利用度,并评价两种制剂生物等效性。结果:单剂量口服试验制剂与进口标准参比制剂后,血浆中双氢可待因的AUC0-12分别为399.51 ng·h·ml-1±67.94 ng·h·ml-1和415.10 ng·h·ml-1±68.31 ng·h·ml-1,Cmax分别为78.08 ng·ml-1±28.18 ng·ml-1和79.73 ng·ml-1±24.35 ng·ml-1,Tmax分别为0.98 h±0.61 h和1.20 h±0.64 h。对乙酰氨基酚的AUC0-12分别为59.41μg·h·ml-1±16.78μg·h·ml-1和58.21μg·h·ml-1±17.07μg·h·ml-1,Cmax分别为15.98μg·ml-1±5.25μg·ml-1和15.89μg·ml-1±6.30μg·ml-1,Tmax分别为0.93 h±0.65 h和1.15 h±0.81 h。相对生物利用度分别为97.2%±14.4%和102.7%±8.3%。试验药双氢可待因和对乙酰氨基酚的AUC0-t90%可信限分别为91.5%-101.2%和99.8%-105.1%,Cmax90%可信限分别为85.6%-109.8%和93.8%-111.4%。结论:两种制剂生物等效。
AIM: To investigate the bioavailability and bioequivalence of paracetamol / dihydrocaleate tartrate tablets in healthy volunteers. Methods: Twenty-two healthy volunteers were randomized single-blind, single-dose, and double-cycle oral administration of the domestic preparation (test preparation) and imported preparation (reference preparation) in a dosage of 20 mg of dihydrocodeine tartrate, acetaminophen 1000 mg, plasma concentrations of 10 time points were determined by high performance liquid chromatography, the main pharmacokinetic parameters and relative bioavailability were calculated using the 3P97 program, and the bioequivalence of the two formulations was evaluated. Results: The AUC0-12 of dihydrocodeine in plasma was 399.51 ng · h-1 ± 67.94 ng · h · ml-1 and 415.10 ng · h, respectively, after single-dose oral test and imported standard reference preparations · Ml-1 ± 68.31 ng · h · ml-1, respectively, and the Cmax values were 78.08 ng · ml-1 ± 28.18 ng · ml-1 and 79.73 ng · ml-1 ± 24.35 ng · ml-1, respectively ± 0.61 h and 1.20 h ± 0.64 h. The AUC0-12 of acetaminophen was 59.41μg · h · ml-1 ± 16.78μg · h · ml-1 and 58.21μg · h-ml-1 ± 17.07μg · h · ml-1 respectively with the Cmax of 15.98 μg · ml-1 ± 5.25μg · ml-1 and 15.89μg · ml-1 ± 6.30μg · ml-1 respectively, with Tmax of 0.93 h ± 0.65 h and 1.15 h ± 0.81 h, respectively. The relative bioavailability was 97.2% ± 14.4% and 102.7% ± 8.3%, respectively. The confidence limits of AUC0-t90% for test drug dihydrocodeine and acetaminophen were 91.5% -101.2% and 99.8% -105.1%, respectively. The Cmax90% confidence limits were 85.6% -109.8% and 93.8% 111.4%. Conclusions: Both formulations are bioequivalent.