YE Mina��ZHU Zhua��FU Qianga��SUN Qiangb��MAO Fengb
a.Department of Pharmacy��b.Department of Breast Surgery��Peking Union Medical College Hospital��Chinese Academy of Medical Sciences-Peking Union Medical College��Beijing 100730��China
Abstract��
OBJECTIVE To evaluate the pharmacokinetic parameters of tegafur being metabolized into fluorouracil(5-FU) in patients with advanced breast cancer,and compare their characteristics of tissue distribution.METHODS 39 Patients with breast cancer were enrolled and received repeated doses of 200 mg tegafur twice daily.Plasma,tumor and adjacent healthy tissue samples were collected.The concentrations of tegafur and its metabolite 5-FU were determined by HPLC.The concentration-time profiles for tegafur and 5-FU were fitted with pharmacokinetic model constructed with characteristic metabolism.The tissue distribution factors for tegafur and 5-FU,and the AUC ratios of tegafur to 5-FU in plasma/tumor/healthy tissue were calculated,respectively.RESULT The AUCall of tegafur in tumor,healthy tissue and plasma were 51.20,59.28 ��g��h��g-1 and 156.44 mg��h��L-1,t1/2 were 11.22,11.30 and 11.92 h,respectively.The AUCall of 5-FU in tumor,healthy tissue and plasma were 4.25,2.87 ��g��h��g-1 and 1.68 mg��h��L-1,respectively.The tissue distribution factors of tegafur were 0.33 in tumor(AUCTumor/AUCplasma) and 0.38 in healthy tissue(AUCH-tissue/AUCplasma).The tissue distribution factors of 5-FU were 2.53 in tumor and 1.71 in healthy tissue.The AUC ratios of tegafur to 5-FU in tumor/healthy tissue/plasma were 8.30,4.84 and 1.07,respectively.CONCLUSION The simulated concentration-time curves of tegafur and its metabolite in plasma and tissue basically describe the activation process of tegafur into 5-FU and 5-FU elimination.The exposures of tegafur in tumor and healthy tissue are similar.The exposure of 5-FU in tumor is found to be 2.53 times as much as that in plasma.It suggests that tegafur is preferentially metabolized into 5-FU in tumor tissue after oral administration.
.Pharmacokinetic Analysis on Tissue Penetration of Tegafur and Tumor-Selective Distribution of 5-FU in Patients with Advanced Breast Cancer [J] Chinese Pharmaceutical Journal, 2007,V42(01): 48-52
2007, Vol. 42 