CAJ | 학술논문

目的建立测定人全血中吲达帕胺(IND)药物浓度的 HPLC-UV 法,研究高血压患者和健康受试者口服(po)IND 片后体内药动学参数的差异.方法8例高血压患者及8例健康自愿者 po IND 片5 mg,采用 HPLC-UV 法(Luna C18色谱柱,pH4磷酸盐缓冲液-乙腈-甲醇(55∶40∶5)与甲醇梯度洗脱,240nm 波长检测)测定给药后不同时间点的全血中 IND 浓度,采用 DAS 2.3程序软件对血药浓度数据进行房室模型的判别,选择最佳权重、最佳房室模型.根据确定的最佳权重和房室模型求出药物动力学参数.结果受试者 po IND 片后的药动学过程符合权重为1的二室模型,以一级动力学方式消除.与健康受试者相比,高血压患者的 AUC、Cmax 及 Tmax 无统计学意义,而 t1/2β与 MRT(0-t)显著降低,CL/F 显著增高.结论建立的全血中 IND 药物浓度的 HPLC-UV 测定法专属性强灵敏度适宜,IND 在高血压患者和健康受试者体内药物动力学过程有着明显的不同;研究 IND 在高血压患者体内的药物动力学过程,能为 IND 临床合理用药提供更为全面的理论依据.
목적건립측정인전혈중신체파알(IND)약물농도적 HPLC-UV 법,연구고혈압환자화건강수시자구복(po)IND 편후체내약동학삼수적차이.방법8례고혈압환자급8례건강자원자 po IND 편5 mg,채용 HPLC-UV 법(Luna C18색보주,pH4린산염완충액-을정-갑순(55∶40∶5)여갑순제도세탈,240nm 파장검측)측정급약후불동시간점적전혈중 IND 농도,채용 DAS 2.3정서연건대혈약농도수거진행방실모형적판별,선택최가권중、최가방실모형.근거학정적최가권중화방실모형구출약물동역학삼수.결과수시자 po IND 편후적약동학과정부합권중위1적이실모형,이일급동역학방식소제.여건강수시자상비,고혈압환자적 AUC、Cmax 급 Tmax 무통계학의의,이 t1/2β여 MRT(0-t)현저강저,CL/F 현저증고.결론건립적전혈중 IND 약물농도적 HPLC-UV 측정법전속성강령민도괄의,IND 재고혈압환자화건강수시자체내약물동역학과정유착명현적불동;연구 IND 재고혈압환자체내적약물동역학과정,능위 IND 림상합리용약제공경위전면적이론의거.
Objective To establish a HPLC-UV assay for the determination of indapamide (IND) in whole blood, and study its pharmacokinetics after per os(po) IND chip. Methods Eight patients with hypertension and 8 healthy volunteers po IND tablets 5 mg, using HPLC-UV method (Luna C18 column, pH4 phosphate buffer-acetonitrile-methanol (55∶40 ∶5) and methanol gradient wash off, detect at the wavelength of 240nm) to measure concentration of IND at different time points after po IND 5mg. The pharmacokinetics parameters of IND were calculated by DAS 2.3 program. Results The concentration-time curve of IND was fitted to a two-compartment model with a weight of 1 and eliminated in a dynamic way. Compared with healthy volunteers, there was no statistically significant with the parameter of AUC, Cmax and Tmax in patients with hypertension, but t1/2β and MRT (0-t) significantly reduced, CL/F was significantly increased. Conclusion The method was convenient, accurate and specific. It was suitable for the study on pharmacokinetics of IND in patients with hypertension. Some pharmacokinetics parameters were defferent between patients with hypertension and healthy volunteers after po 5 mg IND. To studies the pharmacokinetics in patients with hypertension after po IND, will provide a more comprehensive theory for clinical use of IND.