Suein Choi (1,2), Seunghoon Han (1,2), Dong-Seok Yim (1,2)
Catholic university of Korea
Objectives:
Developing the robust population PK model of tacrolimus is challenging and combining available information from various institutions is important. In this study, Tacrolimus PK model was established by model-based stochastic simulation and estimation (SSE) method to build the integrated model which combined published information and observations.
Methods:
2377 concentration data (n=259) of 3 institutions were collected and combined with the virtual dataset simulated from the model in literature. The simulation and dataset integration were repeated 500 times and integrated datasets were analyzed using nonlinear mixed effect model analysis. As population/individual parameters were estimated for each dataset, 500 sets of parameters were estimated, and the medians were considered as final parameters. For patients with long observation(>2yrs, n=22), half of their samples were used for estimation (training set) and the other half (test set) were used to evaluate predictability of model
Results:
The structural model was a 1 compartment model with 1st-order absorption and elimination. The median of clearance (CL/F), volume of distribution (V/F), and absorption rate (Ka) were 6.23L/h, 307.97L, 3.6/h respectively. POD, Weight, drug and institution were selected as covariate. CL/F increases with POD for 2 weeks and decreases afterward, while V/F decreases with POD for 1 month and increases afterward possibly due to hypercatabolic state after the surgery. Visual predictive check showed the estimate is appropriate. Also, test set data were close to prediction value simulated using individual parameters.
Conclusions:
The integrated population PK model combining both prior information and new data was developed by model-based SSE method showing the possibility of developing integrated population model without the prior raw data.
References:
[1] Population Pharmacokinetic–Pharmacogenetic Model of Tacrolimus in the Early Period after Kidney Transplantation, Han N et al. Basic & Clinical Pharmacology & Toxicology, 2014, 114, 400–406
Reference: PAGE () Abstr 9566 [www.page-meeting.org/?abstract=9566]
Poster: Methodology - Estimation Methods