Abstract: AIM: To investigate the population pharmacokinetic characteristics of capecitabine and its possible influencing factors in Chinese patients of breast cancer.  METHODS: 78 cases of Chinese patients with breast cancer were chosen as the objects in this study. Following treatment with capecitabine (0.6 g, 0.15 g/piece, 4 pieces, orally), blood samples were collected and concentrations of capecitabine in plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. The nonlinear mixed-effects software (NONMEM) was used to analyze the data and the population pharmacokinetic model was constructed accordingly. RESULTS: The final established model of absorption and elimination is one-compartment model. The clearance (CL/F) in pharmacokinetic formula of the model is as follows: CL/F=291×eηCL,i×(CCR÷93.1)0.47. The typical pharmacokinetic parameters of the model are as follows: the clearance (CL/F) is 291 L/h; the apparent volume of distribution (V/F) is 556 L; the absorption rate constant (Ka) is 1.05 h-1. In addition, the elimination of capecitabine can be notably influenced by creatinine clearance rate (CCR). CONCLUSION: The constructed model is stable, which fits features well of the population pharmacokinetics of capecitabine in Chinese patients with breast cancer. The modle can be utilized for the individualized administration plan in clinic.

Key words: capecitabine, population pharmacokinetics model, HPLC-MS/MS, breast cancer