芳维甲酸乙酯在Beagle犬体内的药动学研究  

Study on the Pharmacokinetics of Arotinoid Ethylester in Beagle Dogs

作　　者：杨辉[1] 周远大[1] 何海霞[1] 孙纪红 

机构地区：[1]重庆医科大学附属第一医院药学部,重庆400016 [2]重庆市中医院麻醉科,重庆400011

出　　处：《中国药房》2017年第25期3522-3524,共3页China Pharmacy

摘　　要：目的:研究芳维甲酸乙酯(RO)在Beagle犬体内的药动学特征。方法:18只Beagle犬随机分为高、中、低剂量组(40、20、10 mg/kg),每组6只,ig相应剂量的RO。给药后0.5、1.0、2.0、3.0、4.0、6.0、8.0、12.0、24.0、36.0、48.0、60.0、72.0 h时于小隐静脉采血1 mL,分离血浆,采用反相高效液相色谱法同时测定血浆中RO及其代谢产物芳维甲酸乙酸(RA)的浓度;采用DAS 2.0软件进行拟合,计算药动学参数。结果:RO和RA在犬体内均呈一室模型分布。RO高、中、低剂量组犬体内的cmax分别为(1.42±0.87)、(0.54±0.09)、(0.31±0.05)μg/mL,t1/2z分别为(1.20±0.33)、(1.14±0.45)、(1.90±0.65)h,AUC0-72 h分别为(3.55±0.90)、(0.87±0.50)、(0.92±0.31)μg·h/m L,CL/F分别为(11.99±4.01)、(19.87±10.79)、(12.29±7.57)L/(kg·h);RA高、中、低剂量组犬体内的cmax分别为(32.51±4.04)、(19.87±2.78)、(16.55±4.06)μg/mL,t1/2z分别为(7.27±4.20)、(7.17±4.20)、(10.18±4.01)h,AUC0-72 h分别为(408.14±96.61)、(333.39±61.28)、(286.55±30.96)μg·h/m L,CL/F分别为(1.30±0.53)、(0.76±0.87)、(0.54±0.10)L/(kg·h)。结论:RO口服极易吸收,且消除迅速,其活性代谢产物RA在体内蓄积时间较长。OBJECTIVE： To study the pharmacokinetic characteristics of arotinoid ethyl ester （RO） in Beagle dogs in vivo. METHODS： 18 Beagle dogs were randomly divided into high-dose, medium-dose, low-dose groups （40, 20, 10 mg/kg）, 6 in each group. Rats were intragastrically administrated related doses of RO. Blood sample 1 mL was taken after 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0, 60.0, 72.0 h of administration, and plasma was separated. RP-HPLC was used to determine the concentrations of RO and its metabolite arotinoid acetic acid （RA） in plasma. Using DAS 2.0 software for fitting, pharmacokinetic parameters were calculated. RESULTS： Both RO and RA showed a distribution in one-compartment model in dogs in vivo. The Cmax of RO high-dose, medium-dose, low-dose groups in dogs in vivo were （0.42 ± 0.87）, （0.54 ± 0.09）, （0.31 ± 0.05） μg/mL; t1/2t were （1.20±0.33）, （1.14±0.45）, （1.90±0.65）h; AUC072h were （3.55±0.90）, （0.87±0.50）, （0.92±0.31）ixg.h/mL; and CL/F were （ 11.99 ± 4.01 ）, （ 19.87 ± 10.79）, （ 12.29 ± 7.57 ） L/（ kg. h）. The Cmax of RA high-dose, medium-dose, low-dose groups in dogs in vivo were （32.51 ± 4.04）, （19.87 ± 2.78）, （16.55 ± 4.06） μg/mL; t1/2 were （7.27 ± 4.20）, （7.17 ± 4.20）, （10.18 ± 4.01） h; AUC0-72b were （408.14 ± 96.61）, （333.39 ± 61.28）, （286.55 ± 30.96） μg·h/mL; and CL/F were （1.30 ± 0.53）, （0.76 ± 0.87）, （0.54 ± 0.10） L/（kg·h）. CONCLUSIONS： Orally taking RO is easy to absorb with rapid elimination. Its active metabolite RA has longer accumulation time in vivo.

关 键 词：芳维甲酸乙酯 芳维甲酸乙酸 药动学 BEAGLE犬 反相高效液相色谱法 

分 类 号：R961[医药卫生—药理学] R965[医药卫生—药学]