Effects Of X-ray On The Pharmacokinetics Of Irinotecan Hydrochloride

Objective:The aim of the project was to detect the content of Irinotecan?CPT-11?in rat's plasma and to calculate relevant pharmacokinetics parameters,so that an effect of X-ray on the pharmacokinetics of CPT-11 was developed and discussed.The mechanism of X-ray's influence on CPT-11's pharmacokinetics on molecular level was elaborated through the measurement of the protein and m RNA expression of CYP3A1 and CES1.Methods:A High Performance Liquid Chromatography?HPLC?method was adopted to determine the CPT-11 content in rats'plasma.Samples were analyzed by Sepax GP-C18 chromatographic column?4.6 mm×250 mm,5?m?with a flow phase of 0.05 mMol·L-1 KH2PO4/methanol?45:55,pH=4.0?,a flow rate of 1 mL·min-1,a temperature of 30?,a detection wavelength of 254 nm at 20?L dose.All rats were grouped into Low Drug Contract Group?LC?,Low Drug Low Radiation Group?LLR?,Low Drug High Radiation Group?LHR?,High Drug Contract Group?HC?,High Drug Low Radiation Group?HLR?,and High Drug High Radiation Group?HHR?.All rats?except contract groups?were exposed to X-ray,followed by vein injection at thigh after 24h.Relevant parameters were calculated.Levels of CYP3A1and CES1 protein and mRNA were accessed by ELISA and RT-PCR respectively.Results:The pharmacokinetics parameters of rats in LC,LLR,LHR,HC,HLR,HHR groups were as follows:t_1/2/2 were 6.37±1.00,11.43±4.11,6.76±0.83,7.14±1.00,7.16±0.55,6.01±0.81 h;AUC_?0^t?were 67.15±8.67,59.83±5.80,40.96±8.49,145.84±4.60,120.37±15.79,95.73±19.10 mg/L*h,CL were 0.40±0.05,0.38±0.06,0.64±0.10,0.37±0.02,0.46±0.06,0.60±0.10 L/h/kg and MRT_?0-t?were6.49±1.30,7.31±1.23,5.95±1.07,7.16±0.67,7.31±0.16,6.50±0.75 h respectively.In addition,the protein and mRNA expression of CYP3A1 and CES1 have risen distinctively?P<0.05?,compared with control group.Discussion:The HPLC method used in this experiment was suitable for CPT-11concentration detection in rats'plasma,with which a distinctive effect of pharmacokinetics parameters of CPT-11 was discovered.Therefore,a mechanism of up-regulation in CYP3A1 and CES1 protein and gene expression was predicted.