Application of Fourier amplitude sensitivity test in Chinese healthy volunteer population pharmacokinetic model of tacrolimus

In this study, we evaluated the influence of different variance from each of the parameters on  the output of tacrolimus population pharmacokinetic (PopPK) model in Chinese healthy volunteers, using Fourier amplitude sensitivity test (FAST).  Besides, we estimated the index of sensitivity within whole course of   blood sampling, designed different sampling times, and evaluated the quality of parameters’ and the efficiency of prediction.  It was observed that besides CL₁/F, the index of sensitivity for all of the other four parameters (V₁/F, V₂/F, CL₂/F and k_a) in tacrolimus PopPK model showed relatively high level and changed fast with the time passing.  With the increase of the variance of k_a, its indices of sensitivity increased obviously, associated with significant decrease in sensitivity index for the other parameters, and obvious change in peak time as well.   According to the simulation of NONMEM and the comparison among different fitting results, we found that the sampling time points designed according to FAST surpassed the other time points.  It suggests that FAST can access the sensitivities of model parameters effectively, and assist the design of clinical sampling times and the construction of PopPK model.