摘要
[Objectives]To evaluate the acute toxicity and toxicokinetics of Tongguan Powder in rats,and provide references for clinical safe medication.[Methods]The classical acute toxicity test method was used,rats were given different doses of Tongguan Powder through the mouth and nasal cavity to observe the symptoms of toxicity,and make a record of the food intake,weight changes,and death.After the medication,blood was taken from each group of rats at different time points,and the plasma levels of benzoyl aconitine(BA),benzoyl hypaconine(BH)and benzoyl mesaconine(BM)were determined by the liquid chromatography tandem-mass spectrometry(LC-MS/MS),and the toxicokinetic parameters were fitted with the aid of DAS software.[Results]Rats were given Tongguan Powder 3.75 g/kg(equivalent to 54 times the human daily dose)in the nasal cavity of rats.Rats were observed with reactions such as scratching and sneezing;rats were given Tongguan Powder LD50 and 95%confidence limit of 4.15(3.53-4.71)g/kg through the oral administration,which is equivalent to 60 times the human daily dose,rats showed slow weight gain,decreased food intake,decreased voluntary activities,prone,black stools,etc.One hour after nasal administration of Tongguan Powder,the plasma concentration of benzoyl aconitine and benzoyl hypaconine was below the lower limit of detection,and benzoyl mesaconine could not be detected at any time point;one hour after the oral administration of Tongguan Powder,the plasma concentration of the three components reached the maximum,the exposure level of benzoyl hypaconine was higher than that of benzoyl aconitine and benzoyl mesaconine;there was no gender difference in the kinetic parameters.[Conclusions]The toxicity of Tongguan Powder in nasal administration is much lower than that of intragastric administration.The target organs and mechanism of toxicity need to be further studied.
基金
Key Scientific and Technological Innovation Project of Shandong Province,China(2018CXGC1304).
