中国临床药理学与治疗学2012，Vol.17Issue(3)：245-250,6.
五味子甲素对大鼠咪达唑仑及其代谢物1'-羟基咪达唑仑药动学影响
Effects of Schisandrin A on pharmacokinetics of midazolam and its metabolite in rats
摘要
Abstract
AIM: To evaluate whether Schisandrin A (SchA) can modify the pharmaco-kinetic profiles CYP3A substrates-midazolam in male rats. METHODS: The rats were intragas-tric administrated with varied dose SchA or 75 mg/kg ketoconazole for 3 consecutive days. U-sing of single-pass duodenum perfusion and inguinal artery -canulated rats (in vivo), midazolam metabolism was studied under chemical inhibition of CYP3A (ketoconazole) as positive control. Plasma concentrations of midazolam and related metabolites were analyzed by high performance liquid chromatography ( HPLC). RESULTS: The pharmacokinetic parameters of midazolam after coadministration with SchA were as follows: AUQo-o (mg ? L ' ? h)s ( 1. 08 ± 0.29) (negative control) and (1.58 ±0.58) (SchA 8 mg/kg) and (2. 02 ±1.29) (SchA 16 mg/kg) and (2. 22±1.25) (SchA 32 mg/kg) and 3. 34 + 2. 25 (ketoconazole 75 mg/kg) ;CM)1 (mg/L): (1.6 ±0.6) (negative control) and (1. 8±0. 8) (SchA 8 mg/kg) and (2. 2 ±1.2) (SchA 16 mg/kg) and (2. 2 ± 0. 7) (SchA 32 mg/kg) and (2.9 + 1.1) (ketoconazole 75 mg/kg). The pharmacokinetic parameters of 1 -hydroxy midazolam after coadministration with SchA were as follows: AUC(0-t)> (mg · L-1 · h) : (0.61 ±0.17) (negative control) and (0. 40± 0.15) (SchA 8 mg/kg) and (0.39 ±0.20) (SchA 16 mg/kg) and (0. 40±0. 14) (SchA 32 mg/kg) and (0.35 ±0.09) (ketoconazole 75 mg/kg), Cmax(mg/L): (0. 54±0. 13) (negative control) and (0. 42±0.15)(SchA 8 mg/kg) and (0. 39±0. 20) (SchA 16 mg/kg) and (0. 36 ± 0.16) (SchA 32 mg/kg) and (0. 35+0.12) (ketoconazole 75 mg/kg). CONCLUSION- The current results provide direct and explicit evidence that the metabolism of midazolam (a CYP3A substrate) is controlled by SchA in comparison with vehicle-treated rats.关键词
五味子甲素/咪达唑仑/1'-羟基咪达唑仑/药动学/CYP3A4/HPLC法Key words
Schisandrin A/ Midazolam, l'-hydroxy midazolam/ Fharmacokmetics/CYP3A/HPLC method分类
医药卫生引用本文复制引用
辛华雯,李维亮,吴笑春,李罄,余爱荣..五味子甲素对大鼠咪达唑仑及其代谢物1'-羟基咪达唑仑药动学影响[J].中国临床药理学与治疗学,2012,17(3):245-250,6.基金项目
湖北省卫生厅科研基金资助(JX3B38) （JX3B38）
