Abstract: AIM: To analyze and evaluate the accumulation index (R_ac) in clinical pharmacokinetics of multiple dosing administrations in order to obtain one reasonable method. METHODS: The plasma concentration-time data of arteether was simulated for 1000 subjects in multiple doses administration. The 20-40 subjects were sampled for 1000 time by the Boostrap method and values of R_ac were calculated by the AUC, C_max, C_trough and model. The values of R_ac were evaluated by their distributions. RESULTS: The AUC and C_max method were more stable than the C_trough and model method. If the efficacy or toxicity was related with the concentration, it was appropriate to use the C_max method, and if the efficacy or toxicity was related with the time, it was appropriate to use the AUC method. CONCLUSION: The drug accumulation is related with effectiveness and safety, and the reasonable choice of R_ac calculation method should be based on drug and data characteristics.

Key words: Accumulation index, Pharmacokinetics, Multiple doses administration, Toxicity, Pharmacodynamics effect