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雷诺嗪缓释片在中国健康人体内的药代动力学研究
Pharmacokinetic study of ranolazine in Chinese healthy volunteers
- 第三军医大学学报 2019年41卷第2期 页码：177-182
- 作者机构：
1.400038 重庆, 陆军军医大学(第三军医大学)第一附属医院药剂科
2.056001 河北 邯郸, 解放军第980医院邯郸分院药剂科
- 作者简介：
[ 陈勇川, E-mail：zwmcyc@163.com CHEN Yongchuan, E-mail: zwmcyc@163.com
- 基金信息：重庆市社会事业与民生保障科技创新专项项目(CSTC2017shmsA130043)
DOI：10.16016/j.1000-5404.201808200
中图分类号： R944.9;R969.1;R972.3收稿：2018-08-31，
修回：2018-10-10，
纸质出版：2019-01-30
- 稿件说明：
移动端阅览
喻明洁, 向荣风, 熊丽蓉, 等. 雷诺嗪缓释片在中国健康人体内的药代动力学研究[J]. 第三军医大学学报, 2019,41(2):177-182.
Mingjie YU, Rongfeng XIANG, Lirong XIONG, et al. Pharmacokinetic study of ranolazine in Chinese healthy volunteers[J]. Journal of Third Military Medical University, 2019, 41(2): 177-182.
喻明洁, 向荣风, 熊丽蓉, 等. 雷诺嗪缓释片在中国健康人体内的药代动力学研究[J]. 第三军医大学学报, 2019,41(2):177-182. DOI： 10.16016/j.1000-5404.201808200.
Mingjie YU, Rongfeng XIANG, Lirong XIONG, et al. Pharmacokinetic study of ranolazine in Chinese healthy volunteers[J]. Journal of Third Military Medical University, 2019, 41(2): 177-182. DOI： 10.16016/j.1000-5404.201808200.
摘要
目的
2
评价雷诺嗪缓释片单次和多次口服给药后在中国健康人体内的药代动力学特征。
方法
2
采用自身对照试验设计
单次、多次给药组各纳入10例健康受试者
男女各半
单次分3个周期依次服用500、1 000、1 500 mg雷诺嗪缓释片；多次分2个周期依次服用500、1 000 mg雷诺嗪缓释片；采用高效液相色谱-串联质谱(LC-MS-MS)法测定血浆样品中雷诺嗪的浓度
计算主要药代动力学参数。
结果
2
血浆中雷诺嗪浓度线性范围为40~4 000 μg/L
定量下限为40 μg/L
批内、批间精密度均小于15%。单次给药3个不同剂量(500、1 000、1 500 mg)的C
max
分别为(774±157)、(1 818±554)、(2 762± 1 099)μg/L；t
max
分别为(4.9±1.8)、(4.9±2.6)、(4.9±1.5)h；t
1/2z
分别为(8.2±6.
8)、(10.3±8.7)、(9.7±12.0)h；AUC
0-t
分别为(8 470±2 765)、(20 936±6 957)、(32 554±17 780)μg·h/L。多次给药2个不同剂量(500、1 000 mg)C
maxss
分别为(1 826±904)、(3 635±620)μg/L；C
minss
分别为(1 022±3)、(2 282±163)μg/L；C
av
分别为(1 253±634)、(2 615±536)μg/L；AUC
0-t
分别为(22 452±12 359)、(53 232±15 909)μg·h/L；MRT
0-t
分别为(8.7±2.3)、(10.6±2.6)；R
AUC
分别为(3.11±2.60)、(2.86±1.54)。
结论
2
在单次给药试验中C
max
和AUC与剂量呈比例增加
且3个给药剂量有很好的线性关系；多次给药试验发现雷诺嗪在健康人体内有一定的积累。
Abstract
Objective
2
To evaluate pharmacokinetics after administration of ranolazine sustained release tablets at a single and multiple dose to healthy Chinese volunteers.
Methods
2
A self-controlled trial design was used. In the single-time group
10 healthy volunteers
half male and half female
were included
and 500
1 000 and 1 500 mg ranolazine sustained-release tablets were taken sequentially in 3 cycles. For the multiple-dose group
10 individuals of both sexes were enrolled
and 500 and 1 000 mg ranolazine sustained-release tablets were sequentially administered in 2 cycles. The concentration of ranolazine in plasma samples was determined by LC-MS-MS
and the main pharmacokinetic parameters were calculated.
Results
2
The linear concentration of ranolazine in plasma ranged from 40 to 4 000 μg/L
and the LLOQ was 40 μg/L. The intra-assay and inter-assay precision were less than 15%. After single dose
the main parameters in doses 500
1 000
1 500 mg were C
max
: 774±157
1 818±554 and 2 762±1 099 μg/L
respectively;
t
max
: 4.9±1.8
4.9±2.6 and 4.9±1.5 h
respectively;
t
1/2z
: 8.2±6.8
10.3±8.7 and 9.7±12.0 h
respectively; AUC
0-t
: 8 470±2 765
20 936±6 957 and 32 554±17 780 μg·h/L
respectively. After multiple dose
the main parameters in doses 500
1 000 mg were C
maxss
: 1 826±904 and 3 635±620 μg/L; C
minss
: 1 022±3 and 2 282±163 μg/L; C
av
: 1 253±634 and 2 615±536 μg/L; AUC
0-t
: 22 452±12 359 and 53 232±15 909 μg·h/L; MRT
0-t
: 8.7±2.3 and 10.6±2.6; R
AUC
: 3.11±2.60 and 2.86±1.54.
Conclusion
2
In a single administration trial
C
max
and AUC are increased proportionally to the dose
and there is a good linear relationship between the three doses. Multiple dose tests have found that ranolazine has a certain accumulation in the body.
关键词
Keywords
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