%0 Journal Article
%T Population Pharmacokinetic Analysis to Inform Sirolimus Dose Selection in Adult Liver Transplant Patients
%A Ahmed Mansour
%A Omar Saeed
%J Annals of Pharmacy Practice and Pharmacotherapy
%@ 3062-4436
%D 2025
%V 5
%N 2
%R 10.51847/mXLAn8GwTD
%P 88-97
%X Sirolimus is an immunosuppressive agent frequently prescribed following solid organ transplantation. It exhibits a narrow therapeutic index and substantial interpatient pharmacokinetic variability, making it essential to understand the factors contributing to this variability and to develop individualized dosing strategies. This work sought to establish a population pharmacokinetic model of sirolimus in adults following liver transplantation and to use it as a basis for optimizing dose selection according to individual patient factors. A dataset comprising 216 whole-blood sirolimus concentration measurements from 103 adult liver transplant patients was used for the analysis. Potential covariates affecting sirolimus pharmacokinetics were evaluated using a stepwise modeling approach. In addition, Monte Carlo simulations were performed to explore and propose dosing strategies across different patient subgroups defined by relevant covariate levels. A one-compartment model with first-order elimination best described the sirolimus concentration data. Hematocrit (HCT) was identified as a significant covariate affecting apparent clearance. Monte Carlo simulation results suggested that dosing should be adjusted according to HCT levels. In patients with reduced HCT (28%), suitable regimens included 1.5 mg once daily or alternating doses of 1 mg and 1.5 mg once daily. For patients with normal HCT values, recommended options were 1 mg once daily, 2 mg every other day, or alternating 0.5 mg and 1 mg once daily. By analyzing a comprehensive population pharmacokinetic database of sirolimus in adult liver transplant recipients, we identified hematocrit as a major determinant of dosing requirements. We therefore suggest that sirolimus treatment be tailored to individual HCT levels.
%U https://galaxypub.co/article/population-pharmacokinetic-analysis-to-inform-sirolimus-dose-selection-in-adult-liver-transplant-pat-dpvikdxn1xr6qhv