摘要
目的:研究中国健康受试者单次和多次口服阿雷地平(AR)肠溶胶囊后阿雷地平(AR)及其主要代谢产物羟基阿雷地平(AR-M1)的药代动力学特征。方法:36名健康受试者,随机分为3组,平行单次口服5,10和20 mg阿雷地平肠溶胶囊的药代动力学研究,10 mg组受试者继续进行多次口服10 mg,qd,连续7 d的药代动力学研究,采用LC-MS/MS法测定血浆中阿雷地平及其主要代谢产物AR-M1的药物浓度,采用DAS 2.1.1软件计算药代动力学参数。结果:单次口服阿雷地平肠溶胶囊5～20 mg后阿雷地平和AR-M1的消除半衰期(t1/2z)分别约为2.0～2.7 h和3.9～5.6 h;达峰浓度(Cmax)随剂量增加呈线性增加,分别为[(2.12±1.14)～(11.34±5.98)μg.L-1]和[(29.41±9.80)～(111.74±24.03)μg.L-1];血药浓度-时间曲线下面积(AUC)也随剂量增加呈线性增加,阿雷地平和AR-M1的AUC0～t分别为[(6.02±2.96)～(30.33±8.88)μg.h.L-1]和[(156.05±32.24)～(776.00±160.47)μg.h.L-1],AUC0～∞分别为[(6.12±2.98)～(30.53±8.89)μg.h.L-1]和[(159.39±33.23)～(785.53±161.92)μg.h.L-1]。多次口服阿雷地平肠溶胶囊10 mg后阿雷地平和AR-M1的t1/2z分别约为2.5和5.5 h,AUC0～t分别为(18.09±5.42)和(604.46±159.66)μg.h.L-1,AUC0～∞分别为(18.25±5.42)和(611.93±162.81)μg.h.L-1。结论:在5～20 mg剂量范围内阿雷地平和AR-M1呈线性药代动力学特征,10 mg多次给药,阿雷地平和AR-M1的Cmax和AUC均较单次给药显著增加,但未见明显蓄积。
Objective： To determine the pharmacokinetic （PK） characteristics of aranidipine （AR） and its active metabolite hydroxyl-aranidipine （AR-M1） after single and multiple doses of AR enteric capsules in healthy Chinese volunteers. Methods： Totally 36 subjects were randomly assigned to receive AR 5, 10 or 20 mg once for the single dose study. In addition, the subjects in 10 mg group received 10 rag, qd for another 7 days for a multiple dose study. The plasma concentrations of AR and AR-M1 were determined by LC-MS/MS, and the parameters were calculated using DAS 2.1.1 software. Results： The elimination half-life （tl/2z） of AR and AR-M1 after po AR 5 - 20 mg were about 2.0 -2.7 h and 3.9 -5.6 h. Cmax of AR and AR-M1 increased linearly from （2.12± 1.14） to （ 11.34 ±5.98） μg· L^（-1） and （29.41 ± 9.80） to （ 111.74 ± 24.03 ） μg· L^（-1） with the increasing dose. AUC also increased linearly within the dose range of 5 -20 rag. AUC0-t of AR and AR-M1 were [ （6.02 ±2.96） to （30.33±8.88） μg·h·L^（-1）] and [（156.05 ±32.24） to （776.00 ±160.47） μg·h·L^（-1）], and AUC0-∞ were [（6. 12± 2.98） to （30.53 ±8.89） μg·h·L^（-l） and [（159.39 ±33.23） to （785.53 ±161.92） μg·h·L^（-1）, respectively. The pharmaeokinetie parameters of AR and AR-M1 in AR 10 mg multiple doses study were as follows： t1/2, about 2.5 and 5.5 h, AUC0-t（18.09 ±5.42） and （604.46 ±159.66）μg·h·L^（-1）, AUC0-∞ （18.25 ±5.42） and （611.93 ± 162.81） Ixg＇h＇L 1 respectively. Conclusion： AR and AR-M1 exhibit linear pharmaeokinetie profiles in AR dose range from 5 to 20 rag. The Cmax and AUC of multiple-dose regimen are significantly increased compared with the single dose regimen. The accumulation of AR and AR-M1 is not significant.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2012年第15期1782-1786,1791,共6页
Chinese Journal of New Drugs
关键词
阿雷地平
羟基阿雷地平
液相色谱串联质谱法
药代动力学
血药浓度
aranidipine
hydroxyl-aranidipine
liquid chromatography-tandem mass spectrometry
phar-macokinetics
plasma concentration
