单剂量口服匹伐他汀钙片在中国健康志愿者的药代动力学和安全性

目的 研究国产匹伐他汀钙片(降血脂药)在中国健康志愿者体内单次给药的药代动力学特征及安全性.方法 选择中国健康受试者12例,按3×3拉丁方设计,分别单次给予匹伐他汀钙片1,2,4 mg后,采用液相色谱-串联质谱联用法测定不同时间血中匹伐他汀的浓度,以DAS 2.0软件进行数据处理,求算药代动力学参数.结果 3个不同剂量组匹伐他汀的主要药代动力学参数:t_(1/2β)分别为(11.39±7.66),(10.00±7.30),(11.30±7.95)h;t_(max)分别为(0.83±0.29),(0.73±0.20),(0.85±0.46)h;C_(max)分别为(30.48±11.66),(60.80±22.97),(120.98±35.51)ng·mL~(-1);AUC_(0→72h)分别为(93.19±26.61),(179.46±52.86),(364.37±94.74)ng·mL~(-1)·h;AUC_(0→∞)分别为(96.70±27.42),(183.34±53.62),(372.86±95.84)ng·mL~(-1)·h;各剂量组的C_(max)、AuC_(0-72h)、AUC_(0→∞)随剂量的增加而成比例的增大,各组的K_(10)、t_(max)、t_(1/2β)、MRT_(0-72)、MRT_(0→∞)、CL/F、V/F等差异无统计意义.结论 口服给药剂量为1～4 mg时,匹伐他汀钙片在中国健康人体内具有线性药代动力学特征,其代谢特征基本与文献报道一致.

Pharmacokinetics and safety of pitavastatin calcium tablets in Chinese healthy volunteers after a single oral dose administration

Objective To investigate the pharmacokinetics and safety of single dose of pitavastatin calcium tablets in Chinese healthy volunteers. Methods Twelve volunteers were divided into three groups by 3 × 3 de-sign. The drug concentrations of plasma sample from the twelve volun-teers after taking 1, 2 and 4 mg pitavastatin calcium tablets respectively were determined by LC-MS/MS. The pharmacokinetic parameters were calculated by Das 2. 0 software. Results The main pharmacokinetic pa-rameters of pitavastatin after single oral doses (1 mg, 2 mg and 4 mg) were as follows: t_(1/2β) were (11.39±7. 66), (10. 00±7.30), (11.30 ±7.95) h; t_(max) were (0. 83±0. 29), (0. 73±0. 20), (0. 85±0. 46) h; C_(max) were (30.48±11.66), (60.80±22.97), (120.98±35.51)ng ·mL~(-1) ; AUC_(0→72h) were (93. 19 ± 26. 61), (179. 46 ± 52. 86), (364. 37± 94.74) ng·mL~(-1)·h;AUC_(0→∞) were (96.70±27.42),(183.34±53. 62), (372. 86 ± 95.84) ng·mL~(-1)·h. The pharmacokinetic parame-ters such as C_(max), AUC_(0→72h), AUC_(0→∞) directly proportion to doses. There were no significant difference in K_(10), t_(max), t_(1/2β), MRT_(0-72h), MRT_(0→∞), CL/F, WF of three groups by analysis of variance. Conclusion The phannacokinetics of pitavastatin in the dosage of 1-4 mg in human body nearly fit linear dynamic feature. The main pharmacokinetic parameters are similar to those in the reported literature.