Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland.
Department of Pharmacology, Wroclaw Medical University, Wrocław, Poland.
Pharmacol Rep. 2017 Oct;69(5):943-952. doi: 10.1016/j.pharep.2017.03.012. Epub 2017 Mar 18.
Statins and benzodiazepines are widely used drugs, especially in ischemic heart disease, where exacerbation caused by anxiety can even lead to cardiac death. There have not been any reports of statin drug interaction with anxiolytics so far, but it is possible that these drugs interact with each other. We examined the effect of chronic oral administration of simvastatin on the anxiolytic activity and pharmacokinetics of diazepam in rats.
Studies were conducted on male Wistar Han rats treated with simvastatin (2.5, 5, 10, 20mg/kg) for 4-6 weeks, and/or diazepam (2.5, 5, 10mg/kg) administered once on the day of the study. Evaluation of potential pharmacodynamic interaction was based on the behavioral tests: elevated plus maze (EPM) test and the Vogel conflict test (VCT). The assessment of the potential pharmacokinetic interaction was based on measurements of concentrations of diazepam and its metabolites in the blood of animals.
Diazepam 5 and 10mg/kg given together with simvastatin 10 and 20mg/kg showed no anxiolytic effect in the EPM test. In the VCT diazepam combinations with simvastatin did not produce any anxiolytic effect either, with an exception of the co-administration of diazepam 10mg/kg and simvastatin 10mg/kg. Simvastatin (20mg/kg) significantly reduced the area under curve (AUC) of diazepam by 51.6% and temazepam by 54.6%.
Abolition of diazepam anxiolytic effect during concomitant use of simvastatin is probably caused by diminished bioavailability of diazepam, although pharmacodynamic interaction between these drugs cannot be excluded.
他汀类药物和苯二氮䓬类药物是广泛使用的药物，特别是在缺血性心脏病中，焦虑引起的加重甚至可能导致心脏死亡。到目前为止，还没有他汀类药物与抗焦虑药相互作用的报告，但这些药物可能相互作用。我们研究了辛伐他汀的慢性口服给药对大鼠地西泮的抗焦虑作用和药代动力学的影响。
对接受辛伐他汀（2.5、5、10、20mg/kg）治疗 4-6 周的雄性 Wistar Han 大鼠进行了研究，并且/或者在研究当天给予地西泮（2.5、5、10mg/kg）一次。潜在药效学相互作用的评估基于行为测试：高架十字迷宫（EPM）测试和沃格尔冲突测试（VCT）。潜在药代动力学相互作用的评估基于动物血液中地西泮及其代谢物浓度的测量。
地西泮 5 和 10mg/kg 与辛伐他汀 10 和 20mg/kg 一起给药时，在 EPM 测试中没有显示出抗焦虑作用。在 VCT 中，地西泮与辛伐他汀的组合也没有产生任何抗焦虑作用，除了地西泮 10mg/kg 和辛伐他汀 10mg/kg 的联合给药。辛伐他汀（20mg/kg）显著降低地西泮的曲线下面积（AUC）51.6%和替马西泮 54.6%。
在辛伐他汀同时使用时，地西泮的抗焦虑作用被消除，可能是由于地西泮的生物利用度降低所致，尽管不能排除这些药物之间的药效学相互作用。
