Sensitivity of Estimated Tacrolimus Population Pharmacokinetic Profile to Inaccurate Assumptions about Dose Timing and Absorption: An Investigation in Real-World and Simulated Data

Abstract

A tacrolimus population pharmacokinetic (PK) study with 440 subjects was performed using real world data extracted from electronic heath records (EHRs) to identify patient factors affecting variability in tacrolimus PK parameters. Using last-dose times extracted by our own natural language processing system, medExtractR, we assessed the effects of incorporating last-dose times in the data on tacrolimus PK parameter estimates. The estimates of population level PK parameters were Cl = 24.9 L/h [23.5, 26.3] and V = 6310 L [5461, 7159]. There was no appreciable difference in parameters estimates with vs. without last-dose time incorporated in the data. We also investigated the effects of absorption rate constants that are often fixed at a published value in tacrolimus population PK analysis. Our sensitivity analysis revealed little difference between parameters estimated assuming a range of absorption rate constants.