Simulation of perioperative Ibrutinib withdrawal using a population pharmacokinetic model and sparse clinical concentration data.

Ibrutinib carries a significant bleeding risk, but there is no established protocol for how long to withhold the drug perioperatively based on bleeding risk category. This exploratory study simulated individualized ibrutinib pharmacokinetic profiles in five patients undergoing surgery, using Bayesian estimation within a previously reported population pharmacokinetic model implemented in Phoenix NLME, to model perioperative withdrawal scenarios. No bleeding events occurred after 3-7 days of withdrawal in patients undergoing low-bleeding-risk surgery, but one patient undergoing a higher-risk procedure experienced bleeding, and concomitant isavuconazole (a CYP3A4 inhibitor) markedly increased ibrutinib exposure in one case. The findings suggest that relying on plasma concentration data alone may be insufficient to determine optimal perioperative ibrutinib withdrawal timing.