Aim To measure the penetration of capecitabine from the plasma into tissue and to investigate the pharmacokinetics of its metabolizing into fluorouracil （5-FU） in patients with advanced breast cancer. Methods Twenty-seven patients with breast cancer received repeated doses of 1 255 mg·m^-2 of capecitabine twice daily for 7 d. Blood, tumor, and adjacent healthy tissue samples were collected. The concentrations of capecitabine and its metabolite 5-FU were determined by HPLC. The concentration-time profiles of capecitabine and 5-FU were fitted by pharmacokinetic model. The tissue distribution factors for capecitabine and 5-FU, and the AUC ratios of 5-FU to capecitabine in plasma, tumor or adjacent healthy tissue, were calculated with pharmacokinetic parameters, respectively. Results The Ka of capecitabine was 1.17 h^-1 in plasma, 0. 46 h^-1 in tumor tissue, and 0. 61 h^-1 in healthy tissue. The AUCs of capecitabine were 2. 557 1 μg·mL^-1 ·h, 1. 629 2 μg·g^-1·h and 2. 085 0 μg·g^-1· h, and T1/2 was 0. 782 3 h, 1. 528 1 h and 1. 289 6 h in plasma, tumor, and healthy tissue, respectively. The AUCs of 5-FU were 0.418 7 μg·mL^-1 h, 1.671 7 μg·g^-1·h and 1.020 8 μg·g^-1·h; the T1/2 was 0. 631 3 h ,1.204 1 h and 1.031 2 h in plasma, tumor, and healthy tissue, respectively. The tissue distribution factors of capecitabine were 0. 637 1 in tumor （AUCcap-Tumor/AUCcap-plasma） and 0. 851 4 in healthy tissue （AUCcap-HT/AUCcap-plasma . The tissue distribution factors of 5-FU were 3. 992 6 in tumor （AUC5-FU-Tumor/AUC5-FU-plasma） and 2. 438 0 in healthy tissue （AUC5-FU-HT/AUC5-FU-plasma）. The AUC ratios of 5-FU to capecitabine were 0. 1637, 1. 0261, and 0. 489 5 in plasma, tumor, and healthy tissue, respectively. Conclusion The simulation curves for the disposition of capecitabine and its metabolite 5-FU in plasma and tissue basically describe the activation process of capecitabine metabolizing to 5-FU and 5-FU elimination. There are similar distributions for capecitabine in plasma, tumor, and hea
