OBJECTIVE To measure the
pharmacokinetics for capecitabine metabolizing into fluorouracil (5 FU) in patients with advanced
breast cancer, and compare their characteristics of tissue distribution and tumor selective transformation METHODS 27 patients with breast cancer were enrolled and received repeated doses of 1 255 mg·m -2 capecitabine twice daily Plasma, tumor and adjacent healthy tissue samples were collected The concentrations of capecitabine and its metabolite 5 FU were determined by HPLC The concentration/time curves for capecitabine and 5 FU were fitted with pharmacokinetic model constructed in this study The
tissue distribution factor for capecitabine and 5 FU, and the ratio metabolized from capecitabine into 5 FU in plasma/Tumor/Normal Tissue respectively, were calculated with PK parameters from model simulation RESULTS The ratio metabolized from capecitabine into 5 FU in plasma/Tumor/Healthly Tissue were 0 163, 1 445 and 0 863 respectively The tissue distribution factors for capecitabine were 1 14 in tumor (AUC Tumor /AUC plasma ) and 0 642 9 in healthy tissue (AUC H tissue /AUC plasma ) The tissue distribution factors for 5 FU were 10 14 in tumor (AUC Tumor /AUC plasma ) and 3 41 in healthy tissue (AUC H tissue /AUC plasma ) CONCLUSION The simulation curves of capecitabine and its metabolites in plasma and tissue concentration can basically describe the activation process of capecitabine metabolizing to 5 FU and 5 FU elimination There was similar distribution for capecitabine in plasma, tumor and normal tissue The distribution of 5 FU in tumor was found to be 10 14 times greater than that in plasma and 3 41 times greater than that in normal tissue, respectively It suggests that capecitabine preferentially metabolized to 5 FU in tumor tissue after oral administration of capecitabine