摘要
目的建立人血浆中哌罗匹隆浓度测定的HPLC-MS法,进行人体药动学研究。方法测定健康受试者口服受试制剂(低、中、高3种单剂量和多剂量)后血浆中哌罗匹隆浓度。结果单剂量口服哌罗匹隆(4、8、16mg)后药动学参数:V/F分别为(3623.2±1358.8)、(4224.4±2075.9)和(3712.9±1542.5)L,Tmax分别为(1.92±0.56)、(1.79±0.45)和(1.79±0.62)h,CL/F分别为(390.4±140.0)、(422.99±156.21)和(375.4±131.6)L.h-1,T1/2β分别为(6.60±1.62)、(6.78±1.38)和(6.73±0.99)h,MRT(0-24)分别为(6.58±1.27)、(6.74±0.81)和(6.60±0.58)h,Cmax分别为(1.38±0.38)、(2.79±0.78)和(5.68±1.80)μg.L-1,AUC(0-24),分别为(7.56±2.40)、(15.48±4.23)和(30.88±9.00)μg.h.L-1。哌罗匹隆多剂量(8mg,日3次)药动学参数T1/2β为(6.83±1.71)h,Tmax为(1.90±0.46)h,MRT(0-24)为(6.46±0.58)h,Cssmax为(4.44±0.84)μg.L-1,Cssmin为(1.08±0.48)μg.L-1,Cav为(2.18±0.57)μg.L-1,DF为(1.60±0.35),AUCss(0-8)为(17.42±4.59)μg.h.L-1。结论本方法灵敏高,结果准确,哌罗匹隆在大部分人体内的过程符合二室开放模型,其主要药动学参数与国外文献相近。
OBJECTIVE A method was established to study the pharmacokinetics of perospirone in human plasma. METHODS Healthy volunteers received perospirone tablets (low doses,medium doses,high doses,multi doses), and drug concentrations in plasma were determined by HPLC-MS. RESULTS Pharmacokinetie parameters of perospirone after single oral doses (4,8,16mg) were as follow:V/F: (3623.2 ± 1358.8), (4224.4 ± 2075. 9) and (3712.9 ± 1542.5) L;Tmax were (1.92 ± 0.56), (1.79±0.45) and (1.79 ± 0.62) ; CL/F were (390.4 ± 140.0), (422.99± 156.21) and (375.4± 131.6)L·h^-1,T1/2β were (6.60± 1.62), (6.78 ± 1.38) and (6.73 ±0.99) h;MRT(0-24) were (6.58± 1.27), (6.74 ±0.81) and (6.60±0.58)h;Cmax were (1.38 ± 0.38), (2. 79 ± 0.78) and (5.68 ± 1.80)ug·L^-1; AUC(0- 24) were (7.56 ± 2.40), ( 15.48 ± 4.23) and (30.88 ± 9.00)ug·h·L^-1; the essential pharmacokinetic parameters after oral multi-doses (8mg, t. i. d) were as follow: T1/2β: (6.83 ± 1.71)h, Tmax(1.90 ± 0.46)h, MRT(0- 24) : (6.46 ± 0.58)h, Cssmax: (4.44 ± 0.84) ug·L^-1, Cssmin: ( 1.08 ± 0. 48 )ug·L^-1, Cav: (2.18 ± 0.57 ) ug·L^-1, DF : ( 1.60 ± 0.35 ), AUCss(0 - 8) : ( 17.42 ± 4.59 ) ug·h·L^-1 CONCLUSION The method is sensitive, the results were accurate, a two-compartment open pharmacokinetie model is adapted to of concentration-time data analysis perospirone in plasma, the main pharmacokinetic parameters are similar to those reported abroad.
出处
《海峡药学》
2009年第2期71-75,共5页
Strait Pharmaceutical Journal