重酒石酸卡巴拉汀国产片剂与进口胶囊的生物等效性研究

目的: 研究重酒石酸卡巴拉汀在中国健康受试者体内的药代动力学,并评价其国产片剂(受试制剂)与进口胶囊(参比制剂)的生物等效性。 方法: 采用LC-MS/MS法测定20名健康受试者口服卡巴拉汀制剂后血浆中的卡巴拉汀浓度。采用DAS 2.1.1软件计算主要药动学参数,并评价其生物等效性。色谱条件: 采用Agilent ZORBAX SB-C₁₈色谱柱(150 mm×2.1 mm,5 μm),以甲醇-10 mmol·L^-1醋酸铵(含0.1%甲酸)(50: 50)为流动相,流速0.3 mL·min^-1,柱温35 ℃;质谱条件: 采用离子喷雾离子化源,正离子方式检测,多重反应监测(MRM),用于定量分析的离子反应分别为m/z 251.2→206.3(卡巴拉汀)和m/z 275.2→230.2(氯苯那敏)。 结果: 受试制剂与参比制剂的AUC_0-t分别为(14.36±9.61)和(13.56±8.88) ng·h·mL^-1;C_max分别为(8.03±4.01)和(7.60±3.37) ng·mL^-1;T_max分别为(0.75±0.31)和(0.70±0.26) h;t_1/2分别为(1.12±0.24)和(1.13±0.24) h。以卡巴拉汀计,受试制剂的相对生物利用度为(107.0±16.2)%。 结论: 试验结果表明受试制剂和参比制剂口服后吸收速度和程度相当,具有生物等效性。

Objective: To investigate the pharmacokinetics of rivastigmine tartrate in healthy Chinese volunteers, and evaluate the bioequivalence between its domestic tablet(test formulation) and imported capsule(reference formulation). Methods: The plasma concentrations of rivastigmine were determined using LC-MS/MS method in 20 healthy Chinese volunteers after oral administration of rivastigmine formulation. The main pharmacokinetic parameters of rivastigmine and bioequivalence between the two formulations were calculated by DAS 2.1.1. The separation was achieved on an Agilent ZORBAX SB-C₁₈ column(150 mm×2.1 mm,5 μm), the mobile phase consisted of methanol-10 mmol·L^-1ammonium acetate containing 0.1% formic acid(50: 50) at a flow rate of 0.3 mL·min^-1, and the column temperature was 35 ℃. ESI source was applied and operated in positive ion mode and multiple reaction monitoring(MRM). The ion combination of m/z 251.2→206.3 and m/z 275.2→230.2 was used to qualify rivastigmine and chlorpheniramine respectively. Results: The AUC_0-t was (14.36±9.61) and (13.56±8.88) ng·h·mL^-1, C_max was (8.03±4.01) and (7.60±3.37) ng·mL^-1, T_max was (0.75±0.31) and (0.70±0.26) h, and t_1/2 was (1.12±0.24) and (1.13±0.24) h for the test and reference formulations, respectively. The relative bioavailability of the test formulation was (107.0±16.2)%. Conclusion: The results demonstrate that the test and reference formulations are bioequivalent, and there is no significant difference in the rate or extent of absorption after oral administration.