Effect of X-ray on the pharmacokinetics of icotinib in vivo
Objective:To establish a quantitative LC-MS/MS method for determination of icotinib concentration in rat plasma to investigate the effect of thoracic X-ray irradiation on the pharmacokinetics of icotinib in rats and investigate whether there is radiotherapy-pharmacokinetics(RT-PK)phenomenon for icotinib.Methods:SD rats were randomly divided into control and radiation groups.The radiation groups were irradiated with different dosages of X-ray for different times or at different sites.After 24 hours of recovery,15 mg·kg-1 of icotinib was given to rats by gavage and plasma was collected at different time points.The concentrations of icotinib in the plasma samples were determined by LC-MS/MS,and the pharmacokinetic parameters were calculated.Results:The LC-MS/MS method for determination of icotinib in rat plasma was validated successfully.The results of the pharmacokinetic experiments of icotinib showed that the aera under the curve(AUC)of icotinib of the thoracic radiation group increased with increasing dose of radiation after single irradiation,but there was no statistical difference.The icotinib AUC decreased significantly in the thoracic radiation group(RT2Gy)after radiation for five consecutive days.The Cmax of icotinib decreased significantly in the abdominal irradiation group(RT5Gy),but the other PK parameters did not change significantly.Conclusion:The validated LC-MS/MS method is rapid,accurate,and sensitive and can be applied to determine the concentration of icotinib in rat plasma.The results of pharmacokinetic experiments suggest that the effect of single X-ray radiation on the PK of icotinib is not significant,but multiple thoracic radiation may lead to a decrease in plasma exposure.The dosage of icotinib should be rationally adjusted in clinical therapy.
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