CAJ | 학술논문

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.
목적 연구국산필벌타정개편(강혈지약)재중국건강지원자체내단차급약적약대동역학특정급안전성.방법 선택중국건강수시자12례,안3×3랍정방설계,분별단차급여필벌타정개편1,2,4 mg후,채용액상색보-천련질보련용법측정불동시간혈중필벌타정적농도,이DAS 2.0연건진행수거처리,구산약대동역학삼수.결과 3개불동제량조필벌타정적주요약대동역학삼수:t_(1/2β)분별위(11.39±7.66),(10.00±7.30),(11.30±7.95)h;t_(max)분별위(0.83±0.29),(0.73±0.20),(0.85±0.46)h;C_(max)분별위(30.48±11.66),(60.80±22.97),(120.98±35.51)ng·mL~(-1);AUC_(0→72h)분별위(93.19±26.61),(179.46±52.86),(364.37±94.74)ng·mL~(-1)·h;AUC_(0→∞)분별위(96.70±27.42),(183.34±53.62),(372.86±95.84)ng·mL~(-1)·h;각제량조적C_(max)、AuC_(0-72h)、AUC_(0→∞)수제량적증가이성비례적증대,각조적K_(10)、t_(max)、t_(1/2β)、MRT_(0-72)、MRT_(0→∞)、CL/F、V/F등차이무통계의의.결론 구복급약제량위1～4 mg시,필벌타정개편재중국건강인체내구유선성약대동역학특정,기대사특정기본여문헌보도일치.
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.