中国药师
中國藥師
중국약사
CHINA PHARMACIST
2014年
12期
2007-2010
,共4页
二氢吡啶类钙离子拮抗药%CYP3A4%药物相互作用
二氫吡啶類鈣離子拮抗藥%CYP3A4%藥物相互作用
이경필정류개리자길항약%CYP3A4%약물상호작용
Dihydropyridine calcium antagonist%CYP3A4%Drug interaction
目的：：研究二氢吡啶类钙离子拮抗药(DHPs)中非洛地平、尼卡地平、乐卡地平、硝苯地平对CYP3A4酶活性抑制作用大小,为临床了解DHPs发生药物相互作用的几率大小提供理论基础。方法：采用探针药物法,将经80 mg · kg-1· d-1地塞米松诱导3 d的SD雌性大鼠分为阴性对照组、阳性对照组、4种DHPs实验组,每组6只。氨苯砜为探针底物,HPLC法为检测手段,数据通过WinNonLin药动学分析软件进行模型拟合处理,并通过配对t检验进行统计学分析。结果：阴性对照组与四种DHPs组、阳性对照组氨苯砜的AUC0-24、CL/F值比较有统计学意义(P<0.05)。4种DHPs对氨苯砜的代谢抑制作用大小分别为硝苯地平>尼卡地平>乐卡地平>非洛地平,但差异无统计学意义(P>0.05)。而统计学结果显示阳性对照组、4种DHPs组与阴性对照组的Cmax比较,差异无统计学意义(P>0.05)。结论：虽然不同DHPs对CYP3A4存在不同的抑制作用,但差异在体内表现并不显著,对于非主要通过CYP3A4代谢的共服药物不会产生影响。
目的：：研究二氫吡啶類鈣離子拮抗藥(DHPs)中非洛地平、尼卡地平、樂卡地平、硝苯地平對CYP3A4酶活性抑製作用大小,為臨床瞭解DHPs髮生藥物相互作用的幾率大小提供理論基礎。方法：採用探針藥物法,將經80 mg · kg-1· d-1地塞米鬆誘導3 d的SD雌性大鼠分為陰性對照組、暘性對照組、4種DHPs實驗組,每組6隻。氨苯砜為探針底物,HPLC法為檢測手段,數據通過WinNonLin藥動學分析軟件進行模型擬閤處理,併通過配對t檢驗進行統計學分析。結果：陰性對照組與四種DHPs組、暘性對照組氨苯砜的AUC0-24、CL/F值比較有統計學意義(P<0.05)。4種DHPs對氨苯砜的代謝抑製作用大小分彆為硝苯地平>尼卡地平>樂卡地平>非洛地平,但差異無統計學意義(P>0.05)。而統計學結果顯示暘性對照組、4種DHPs組與陰性對照組的Cmax比較,差異無統計學意義(P>0.05)。結論：雖然不同DHPs對CYP3A4存在不同的抑製作用,但差異在體內錶現併不顯著,對于非主要通過CYP3A4代謝的共服藥物不會產生影響。
목적：：연구이경필정류개리자길항약(DHPs)중비락지평、니잡지평、악잡지평、초분지평대CYP3A4매활성억제작용대소,위림상료해DHPs발생약물상호작용적궤솔대소제공이론기출。방법：채용탐침약물법,장경80 mg · kg-1· d-1지새미송유도3 d적SD자성대서분위음성대조조、양성대조조、4충DHPs실험조,매조6지。안분풍위탐침저물,HPLC법위검측수단,수거통과WinNonLin약동학분석연건진행모형의합처리,병통과배대t검험진행통계학분석。결과：음성대조조여사충DHPs조、양성대조조안분풍적AUC0-24、CL/F치비교유통계학의의(P<0.05)。4충DHPs대안분풍적대사억제작용대소분별위초분지평>니잡지평>악잡지평>비락지평,단차이무통계학의의(P>0.05)。이통계학결과현시양성대조조、4충DHPs조여음성대조조적Cmax비교,차이무통계학의의(P>0.05)。결론：수연불동DHPs대CYP3A4존재불동적억제작용,단차이재체내표현병불현저,대우비주요통과CYP3A4대사적공복약물불회산생영향。
Objective:To study the inhibition effects of four dihydropyridine calcium antagonists felodipine, nicardipine, lercani-dipine and nifedipine on CYP3A4 enzyme to provide the theoretical basis for the understanding of the drug interactions between dihydro-pyridine calcium antagonists and other drugs. Methods:Using the probe drugs method, the SD female rats induced by 80 mg·kg-1 · d-1 dexamethasone for three days were divided into the negative control group, positive control group, four DHPs groups with six ones in each. Dapsone was used as the probe substrate, and the concentration was determined by HPLC. Data analysis software WinNonLin was used in the pharmacokinetic model fitting process and the paired t-test was used in the statistical analysis. Results: AUC0-24 and CL/F of dapsone in the negative control group showed statistically significant differences when compared with those in the four DHPs groups and the positive group (P<0. 05). Although the inhibition effect of the four DHPs was in the order of nifedipine inhibition >nicardipine > lercanidipine > felodipine, the difference was not statistically significant (P>0. 05). Cmax of dapsone in the DHPs groups and the positive group had no statistically significant difference when compared with that in the negative control group ( P>0. 05). Conclusion:Although there are different inhibition effects on CYP3A4 among the four DHPs, the differences are not significant in vivo, and there is no influence on the combination drugs which is not mainly metabolized by CYP3A4.
