Abstract: AIM: The nonlinear mixed effect model (NONMEM) was applied in the analysis of Traditional Chinese Medicine (TCM) formula, based on the data of different compatibility of Zexie Tiaozhi granule in treatment of hyperlipidemia rat model. The compatible regularity of Zexie Tiaozhi granule was evaluated quantitatively and the result can be used as a reference to formula optimization. METHODS: The four main compositions of Zexie Tiaozhi granule were combined in uniform design and analyzed by NONMEM. The TG in serum was treated as the pharmacodynamics index.RESULTS: Final model suggested that X₁ was the primary effective composition and X₃ was an antagonistic composition. The dose-effect relationship of X₂ and X₄ was not clear, and the efficacy was mainly expressed in the interaction between compositions. Based on the above, we recommended that the formula will perform maximum efficacy when X₁, X₂ and X₄ take the maximum dose and X₃ take the minimum dose. CONCLUSION: The application of NONMEM in analysis of TCM formula can investigate the interactions among compositions and the random effects like inter individual and intra individual variations comprehensively, which can provide vast quantities of information.

Key words: Multiple regression, Nonlinear mixed effect model, Formula optimization, Simulation