卢帕他定片在中国健康人体的药动学

Study on pharmacokinetics of rupatadine tablet in Chinese healthy volunteers

目的研究卢帕他定片在中国健康人体的药动学特征。方法以卡马西平为内标,色谱柱为inspire C18(2)(150 mm×4.6 mm,5μm),以乙腈:2 mmol·L-1乙酸铵溶液(65:35,V/V)为流动相,流速:0.8 mL·min^(-1);质谱检测卢帕他定和内标卡马西平离子对分别为m/z 416.1→282.1,237.2→194.1。36名健康受试者随机分为低、中、高3个剂量组,每组12人(男女各半),分别单次口服卢帕他定片10 mg、20 mg、40 mg,采用液相色谱-串联质谱法测定给药后不同时间点血浆中卢帕他定的浓度并计算药动学参数。结果人血浆中卢帕他定的最低定量限为0.05μg·L^(-1),在0.05～40μg·L^(-1)范围内线性关系良好,批内及批间精密度(RSD)均小于15%。主要药动学参数如下:ρ_(max)分别为(16.88±8.10)、(30.27±12.10)和(63.87±27.49)μg·L^(-1);t_(max)分别为(0.94±0.39)、(1.00±0.00)和(0.88±0.38)h;t_(1/2)分别为(11.46±3.01)、(8.42±1.65)和(9.06±2.30)h;AUC_(0-t)分别为(46.84±22.15)、(86.16±19.22)和(189.91±59.52)h·μg·L^(-1);AUC_(0-∞)分别为(50.00±23.83)、(88.53±19.49)和(196.13±60.87)h·μg·L^(-1)。结论低、中、高3个剂组中卢帕他定在人体内的AUC_(0-t),AUC_(0-∞)和ρ_(max)均与剂量呈线性关系。

AIM To study the pharmacokinetics of rupatadine tablet in chinese healthy volunteers. METHODS The chromatographic separation was achieved on a inspire C18 （2） （150 mm × 4.6 mm, 5μm）, using a mixture of methanol and aqueous 2 mmol·L-1 ammonium acetate buffer acid （65 ： 35, V/V） as mobile phase at a flow rate of 0.8 mL·min-1. The detection was carried out by means of electrospray ionization mass spectrometry in positive ion mode. MS was performed in the selected reaction monitoring mode using rupatadine at m/z 416.1 → 282.1 for carbamazepine and m/z 237.2 → 194.1 for internal. Thirty-six healthy volunteers were randomly divided into three groups with 12 volunteers in each group （6 males and 6 females）. The three groups received rupatadine tablet at single dose of 10, 20 and 40 mg, respectively. The concentrations of rupatadine in human plasma at different time were determined by high pressure liquid chromotorgraphy mass spectrometry and the pharmacokinetic parameters were calculated. RESULTS The limit of quantitation （LOQ） of rupatadine was 0.05 μg·L-1 and the calibration curve was linear over the range of 0.05 - 40 μg·L-1. The intra- and intra-batch precision （RSD） values were less than 15%. The pharmacokinetic parameters were as follows： ρmax were （16.88 ± 8.10）, （30.27 ± 12.10） and （63.87 ± 27.49） μg·L-1; tmax were （0.94±0.39）, （1.00 ± 0.00） and （0.88±0.38） h; t1/2 were （11.46±3.01）, （8.42 ± 1.65） and （9.06 ± 2.30） h; AUC 0-twere （46.84±22.15）, （86.16 ± 19.22） and （189.91±59.52） h·μg·L-1; AUC0-∞were （50.00±23.83）, （88.53±19.49） and （196.13 ± 60.87） h·μg·L-1. CONCLUSION The values of AUC0-t, AUC0-∞ andρmax were linear in the dose range form 10 mg to 40 mg.