盐酸吡格列酮和阿托伐他汀钙的体外代谢相互作用研究  

Metabolic interactions between Pioglitazone hydrochloride and Atorvastatin calcium in rat liver microsomes

作　　者：陈和莉[1] 杨付英[1] 张文萍[2,3] 杨文成[1] 付岩[1] 党宏万[2,3] 

机构地区：[1]宁夏医科大学药学院,宁夏银川750004 [2]宁夏医科大学总医院药剂科,宁夏银川750004 [3]宁夏医科大学总医院临床药理研究室,宁夏银川750004

出　　处：《华西药学杂志》2013年第2期152-155,共4页West China Journal of Pharmaceutical Sciences

基　　金：宁夏自然科学基金资助项目(批准号:NZ1205)

摘　　要：目的采用HPLC法测定体外盐酸吡格列酮(Pio)、阿托伐他汀钙(Atv),并研究PIO和Atv在大鼠肝微粒体(RLM)中的代谢相互作用。方法用钙沉淀法制备RLM。HPLC采用Hydro-RP 80A C18柱(150 mm×4.6 mm,4μm),流动相为乙腈-水(含3 mL.L-1冰乙酸,1 mL.L-1三乙胺,用25%氨水调pH5.15)(55∶45),流速1 mL.min-1,PIO检测波长240 nm,Atv检测波长246 nm,柱温25℃。体外一定条件下孵化后,绘制PIO、Atv的药物代谢时间曲线,比较单独孵化和共同孵化药物代谢率的变化。结果 Pio和Atv分别在5～240μmol.L-1(r=0.9995)、1～150μmol.L-1(r=0.9997)线性关系良好;Pio、Atv日内、日间RSD分别低于3.79%、3.20%、4.07%、5.25%;Pio低、中、高浓度的萃取回收率分别为104.64%、108.20%、91.15%;Atv低、中、高浓度的萃取回收率分别为100.74%、107.45%、105.27%。在蛋白质浓度为0.5 mg.mL-1时,体外Pio、Atv单独孵化60 min后,代谢率分别为42.75%、26.32%,一同孵化后,代谢率分别降至27.57%、8.96%。结论所用方法灵敏、准确,能用于Pio和Atv在RLM中的代谢研究。体外PIO、Atv同时孵化时,两药产生相互抑制作用。OBJECTIVE To establish an HPLC method for determination of Pioglitazone hydrochloride（Pio） and Atorvastatin calcium （Atv）, and to investigate the interactions between Pio and Atv in rat liver microsomes. METHODS A calcium precipitation method was utilized to prepare rat liver microsomes（ RLM ）. The HPLC method with Hydro - RP 80A - C18 column and a mobile phase made up of acetonitrile -water（including 3 mL·L^-1 glacial acetic acid and 1 mL·L^-1 triethylamine, 25% ammonia to adjust pH to 5.15） （55：45） ,a flow rate at 1.0 mL·min^-1 and the detection wavelength at 240 nm for Pio,246 nm for Atv, a column temperature at 25℃, was established for the determination of Pio and Atv. The metabolism - time profiles were constructed after incubation under certain conditions, and the metabolic percentage of concurrent Pio and Atv was compared with that of Pio or Atv alone. RESULTS The calibration curves of Pio and Atv were linear in the range of 5～240 μxmol·L^-1（r=0.9995） and 1～150 μmol·L^-1（r=0.9997）, respectively. The intra - day and inter - day RSD of Pio were less than 3.79% and 3.20% ,while those of Atv were less than 4.07% and 5.25%. The extraction recoveries of Pio in low,middle,high concentrations were 104.64%, 108.20% ,91.15% ,while those of Atv were 100.74% , 107.45% , 105.27%. When the RLM protein concentration was diluted to 0.5 mg. mL^-1, Pio or Atv alone was eliminated about 42.37% or 26.32% after incubation for 60 min,the depletion percentage of concurrent Pio and Atv after incubation reduced to 27.57% and 8. 96% ,respectively. CONCLUSION The method was sensitive and accurate,and can be used to study the metabolism of Pio and Atv in vitro. Concurrent Pio and Atv after incubation appeared to significantly lower metabolism compared with Pio and Atv.

关 键 词：盐酸吡格列酮 阿托伐他汀钙 大鼠肝微粒体 高效液相色谱法 代谢相互作用 

分 类 号：R96[医药卫生—药理学]