Metabolism of voriconazole injection with different preparation processes in rats
Objective To analyze the metabolism status of voriconazole injection with different prepara-tion processes in rats.Methods A total of 16 male Sprague-Dawley rats were divided into two groups according to the random number table method.One group received the domestically-produced voriconazole injection(Sichuan Meidakang Huakang Pharmaceutical Co.,Ltd.),while another group received the imported voriconazole injection(Pfizer Pharmaceuticals Ltd.),both through tail vein injection,at a dose of 40 mg/kg.High-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)was used to determine the blood concentration of voriconazole injection at 5,30,60,120,240,360,480,720 and 1 440 min in different preparation processes.DAS2.0 pharmacokinetic software was adopted to analyze the blood concentration-time data of voriconazole injec-tion,and the differences in plasma pharmacokinetic parameters of voriconazole injection with different preparation processes.Results There were no statistically significant differences in the time of main pharmacokinetic param-eters reaching the maximum plasma concentration(Tmax),maximum plasma concentration(Cmax),clearance rate(CL),the area under the 24 h drug concentration-time curve(AUC 0～24 h)and mean retention time(MRT)of do-mestic and imported voriconazole injections[(5.00±0.10)min vs(5.00±0.20)min,(28.4±2.4)μg/ml vs(30.1±2.3)μg/ml,(3.5±1.6)ml·h-1·kg-1 vs(2.4±0.6)ml·h-1·kg-1,(249±27)μg·h-1·ml-1 vs(233±20)µg·h-1·ml-1,(7.7±1.3)h vs(6.8±1.0)h](P＞0.05).Most tissues gradually decreased at 480 min after administration,and the main organs and tissue drug concentrations were consistent with plasma drug elimination.Conclusion The pharmacokinetic pa-rameters of voriconazole injection with different preparation processes are similar in rats,and there is no signifi-cant difference in exposure in different organs and tissues.Different preparation processes do not substantially change the pharmacokinetics of voriconazole
VoriconazoleRatsMetabolismHigh-performance liquid chromatography-tandem mass spectrometry
万方数据
维普
