TY  - JOUR
T1  - Population Pharmacokinetic Analysis to Inform Sirolimus Dose Selection in Adult Liver Transplant Patients
A1  - Ahmed Mansour
A1  - Omar Saeed
JF  - Annals of Pharmacy Practice and Pharmacotherapy
JO  - Ann Pharm Pract Pharmacother
SN  - 3062-4436
Y1  - 2025
VL  - 5
IS  - 2
DO  - 10.51847/mXLAn8GwTD
SP  - 88
EP  - 97
N2  - 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.
UR  - https://galaxypub.co/article/population-pharmacokinetic-analysis-to-inform-sirolimus-dose-selection-in-adult-liver-transplant-pat-dpvikdxn1xr6qhv
ER  -