Objective: to establish and validate a new total statistical moment similarity model (TSMSM) for qualitatively and quantitatively evaluating pharmacokinetic behaviors.Methods: By statistical moment theory (SMT) the total statistical moment (TSM) parameters of pharmacokinetic profiles had been elucidated to further diverted into normal distribution probability density function, and thereby to establish the TSMSM for total pharmacokinetic profile evaluations.The validation trial was designed to self-control test of midazolam pharmacokinetic interaction by befor and after taking flucloxacillin in severe case dose (0.5g of flucloxacillin 4 times per day, consecutively administered for 6 days).Twelve healthy subjects were enrolled in the study.Blood samples were collected at regular time intervals.The midazolam and 1-hydroxymidazolam in plasma were determined by RP-HPLC assay.Results: It had been established the TSMSM, for quantitative analyses, as AUCT, total area under curves of all pharmacokinetic profiles; for qualitative analyses, as Su, TSM similarity (TSMS), and as DT, total mean variability; as 1-Su, total variabl probability; as 1-β (α), total variable confident probability.By the model we had analyzed the TSMSM parameters of midazolam pharmacokinetic interaction before and after toking flucloxacillin, the Su, DT, 1-Su, 1-β (α), AUCT∞were 0.9582, 0.0525,4.18%, 2.82% (α=0.05), 334.3±334.1 ng·h·ml-1 (before) and 206.9±172.2 ng·h·ml-1 (after) respectively, and of the 1-Hydroxymidazolam these were 0.6920, 0.396, 30.8%, 5.89% (α=0.02S), 1364±810.7 ng·h·ml-1 (before) and 1637±632.6 ng·h·ml-1 (after) respectively.Conclusion: The TSMSM can be used to qualitatively quantitatively characterize and analyse pharmacokinetic profiles.In clinical severe case dose there was a few induction to CYP3A by flucloxacillin that there is at least 30.80% of metabolic behaviours in change with 38.11% of bioavailability on decrease that takes effects to flucloxacillin metabolism for liver injury.