TY  - JOUR
T1  - Population Pharmacokinetics of Sirolimus in Adult Liver Transplant Recipients: Hematocrit-Guided Dosing Recommendations from a Large Cohort
A1  - Elena Russo
A1  - Matteo Rossi
A1  - Nicola Gallo
JF  - Pharmaceutical Sciences and Drug Design
JO  - Pharm Sci Drug Des
SN  - 3062-4428
Y1  - 2023
VL  - 3
IS  - 1
DO  - 10.51847/ab1Lsk1aJD
SP  - 117
EP  - 127
N2  - Sirolimus is widely prescribed as an immunosuppressive agent following solid organ transplantation. Its therapeutic index is narrow and exposure is highly inconsistent across individuals, highlighting the need to clarify the contributors to this variability and create patient-specific dosing strategies. This work sought to conduct a population pharmacokinetic (PK) evaluation of sirolimus in adult recipients of liver transplants and to formulate dosage recommendations tailored to patient-level characteristics. A dataset of 216 whole-blood sirolimus concentration measurements from 103 adult subjects was used. Potential PK-related covariates were assessed through a stepwise selection procedure. Monte Carlo simulations were applied to propose dosage options for patients across different covariate categories.

A one-compartment structure with first-order elimination most accurately described the observations. Hematocrit (HCT) was found to significantly affect sirolimus apparent clearance. Monte Carlo simulations indicated that individuals with a low HCT of 28% should receive 1.5 mg qd or 1 mg qd alternated with 1.5 mg qd. For those with normal HCT values, suggested regimens were 1 mg qd, 2 mg qod, or 0.5 mg qd alternating with 1 mg qd. Drawing from the largest population PK dataset of sirolimus in adult liver transplant patients available so far, we propose HCT-guided dosing regimens for this population.
UR  - https://galaxypub.co/article/population-pharmacokinetics-of-sirolimus-in-adult-liver-transplant-recipients-hematocrit-guided-dos-mysrziozic0bfs2
ER  -