洛伐他汀缓释片在人体内的药代动力学研究  

Pharmacokinetic studies on the extended-release tablets of lovastatin in human volunteers

作　　者：孙建国[1] 翁合霞[2] 王广基[1] 李鹏[1] 李昊[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室,南京210038 [2]南阳医学高等专科学校,南阳473058

出　　处：《中国药科大学学报》2006年第5期461-465,共5页Journal of China Pharmaceutical University

基　　金：国家高技术研究发展计划("八六三"计划)资助项目(No.2003AA2Z347A;2005AA2Z3C70)~~

摘　　要：目的：研究洛伐他汀缓释片在人体内单次和多次口服给药后的药代动力学过程。方法：采用LC-MS／MS方法测定人血浆中洛伐他汀的浓度。采用正离子方式检测；扫描方式为选择离子反应监测（SRM）。20名男性健康受试者随机鼠交叉单次（40mg）或多次（20mg×6）口服洛伐他汀缓释片和普通制刺海立片，并于相应的时间点取血测定血浆中的药物裂度。结果：所建立的LC-MS／MS方法的线性范围为0．05～10．0ng／mL，最低检测浓度为0．05ng／mL。以海立片为参比对照，用面积法估算的单次和多次给药后洛伐他汀缓释片中洛伐他汀的相对生物利用度分别为（148．5±43．1）％和（140．7±32．8）％。估算单次给药后海立片和洛伐他汀缓释片的人体内洛伐他汀的MRT为（14．61±7．27）h和（29．72±17．22）h；tmax为（4．2±2．1）h和（12．3±7．5）h；cmax为（1．98±1．01）ng／mL和（1．64±0．62）ng／mL；t1／2为（12．16±5．18）h和（18．17±10．78）h。海立片和洛伐他汀缓释片的稳态药物浓度分别为（0．57±0．27）ng／mL和（0．80±0．43）ng／mL，波动度分别为（2．64±1．10）和（0．97±0．36）。结论：单剂量给药后洛伐他汀缓释片与海立片相比，产生的cmax比较平稳，tmax延迟，两种给药方式洛伐他汀缓释片的吸收程度均高于普通制剂。Aim：To study the pharmacokinetics of lovastatin after a single and multiple oral doses of extended-release lovastatin tablets in 20 healthy Chinese volunteers by LC-MS/MS. Methods： Lovasatatin is quantitatively determined by LC-MS/MS using positive ion detection with selected reaction monitoring （SRM）. Extended-release or convention tablets were given to 20 healthy volunteers single dose（40 mg）or multiple doses （20 mg×6） in a two-way crossover design. Blood was drawn at different intervals after treatment. Results： The LC-MS/MS method was proved to be linear over the range of 0.05 - 10.0 ng/mL of lovastatin with limit of quantitation of 0.05 ng/mL. Compared with conventional tablet,the relative bioavailability of lovastatin ER is about （ 148.5 ± 43.1 ） % and （ 140.7 ± 32.8） % after single or multiple doses, respectively. The pharmacokinetic parameters of lovastatin after single dose were as follows ： MRT were （ 14.61±7.27） h and （29.72 ± 17.22） h, t max were （4.2±2.1 ） h and （ 12.3 ±7.5 ） h, c max were （1.98±1.01）ng/mL and （1.64 ± 0.62） ng/mL, and tl/2 were （12.16± 5.18）h and （18.17 ± 10.78）h for conventional tablet and lovastatin ER, respectively. The mean steady state concentrations （css） of lovastatin after six consecutive days treatment with the two formulations were （0.57 ± 0.27） and （0.80 ±0.43） ng/mL with fluctuate degree （DF） of 2.64±1.10 and 0.97±0.36, respectively. Conclusions： Compared with the conventional tablet, the lovastatin ER shown a delayed tmax, lower Cmax and higher bioavailability.

关 键 词：洛伐他汀 缓释片剂 药代动力学 LC-MS/MS 

分 类 号：R96[医药卫生—药理学]