硫酸氢氯吡格雷片在中国健康人体的药代动力学和相对生物利用度研究

Pharmacokinetics and relative bioavailability of clopidogrel bisulfate tablets in Chinese healthy volunteers

目的研究硫酸氢氯吡格雷片在中国健康人体的药代动力学和相对生物利用度。方法 24名健康受试者采用自身对照、随机交叉给药法,单次空腹口服硫酸氢氯吡格雷片参比和受试药物各150 mg。用液相色谱-质谱联用法(LC-MS/MS)测定血浆中氯吡格雷和氯吡格雷羧酸盐代谢物的血药浓度,计算两种药物的药代动力学参数和相对生物利用度。结果血浆中氯吡格雷受试药物和参比药物tmax分别为(1.03±0.36),(1.11±0.41)h;Cmax分别为(2.90±1.68),(3.05±1.63)ng·m L-1;t1/2分别为(3.50±1.19),(3.22±0.66)h;AUC0-t分别为(8.75±5.10),(9.26±5.36)ng·h·m L-1;AUC0-∞分别为(9.52±5.64),(9.97±5.88)ng·h·m L-1;平均相对生物利用度为(98.40±24.30)%。血浆中氯吡格雷羧酸盐代谢物,tmax分别为(0.98±0.72),(0.91±0.40)h;Cmax分别为(4799±1569),(4697±1856)ng·m L-1;t1/2分别为(7.24±1.56),(7.25±1.38)h;AUC0-t分别为(13043±3845),(13707±4007)ng·h·m L-1;AUC0-∞分别为(13933±4242),(14596±4172)ng·h·m L-1;平均相对生物利用度为(95.90±13.50)%。结论两种氯吡格雷和氯吡格雷羧酸盐代谢物具有生物等效性。

Objective To evaluate the pharmacokinetics and relative bioavailability of clopidogrel bisulfate tablets in healthy volunteer. Methods A single oral doses of 150 mg （reference and test） were given to 24 healthy volunteers according to an open randomized crossover design. The concentrations of clopidogrel and its carboxylic acid metabo- lite of reference and test tablets in plasma were determined by LC - MS/ MS. Results The pharmacokinetic parameters for clopidogrel of the two preparations were as follow： t of test drug and reference drug were （1.03 ± 0.36）, （1.11 ± 0.41） h, Cmax were （2.90 ± 1.68）, （3.05 ±1.63） ng ·mL^-1, t1/2 were （3.50±1.19）, （3.22±0.66） h, AUC0-t were （8.75 ±5.10）, （9.26 ±5.36） ng ·h·m L^-1, AUC0-∞ were （9.52 ±5.64）, （9.97 ±5.88） ng ·h·m L^-1. The relative bioavailability of clopidogrel were （98.40 ± 24. 30） %. The pharmaco- kinetic parameters for clopidogrel carboxylic acid metabolite of the two preparations were as follow： tmax of test drug and reference drug were （0.98 ± 0.72）, （0.91 ± 0.40） h, Cmax were （4799 ± 1569）,（4697 ± 1856） ng ·mL^-1, t1/2 were （7. 24 ± 1.56 ）, （7.25 ± 1.38 ） h, AUC0-1 were （ 13042 ± 3845 ）, （13707±4007） ng·h·m L^-1, AUC0-∞ were （13933 ±4242）, （14595 ±4172） ng ·h·m L^-1. The relative bioavailability of clopidogrel carboxylic acid metabolite were （95.90 ± 13.50） %. Conclusion Main pharmacokinetic parameters for elopidogrel and its earboxylic acid metabolite were tested to be bioequivalent.