Physiologically-Based Pharmacokinetic Modeling of Blood Clearance of Liver Fluorescent Markers for the Assessment of the Degree of Hepatic Ischemia-Reperfusion Injury.
Annu Int Conf IEEE Eng Med Biol Soc
; 2023: 1-6, 2023 07.
Article
en En
| MEDLINE
| ID: mdl-38082711
ABSTRACT
During liver transplantation, ischemia-reperfusion injury (IRI) is inevitable and decreases the overall success of the surgery. While guidelines exist, there is no reliable way to quantitatively assess the degree of IRI present in the liver. Our recent study has shown a correlation between the bile-to-plasma ratio of FDA-approved sodium fluorescein (SF) and the degree of hepatic IRI, presumably due to IRI-induced decrease in the activity of the hepatic multidrug resistance-associated protein 2 (MRP2); however, the contribution of SF blood clearance via the bile is still convoluted with other factors, such as renal clearance. In this work, we sought to computationally model SF blood clearance via the bile. First, we converted extant SF fluorescence data from rat whole blood, plasma, and bile to concentrations using calibration curves. Next, based on these SF concentration data, we generated a "liver-centric", physiologically-based pharmacokinetic (PBPK) model of SF liver uptake and clearance via the bile. Model simulations show that SF bile concentration is highly sensitive to change in the activity of hepatic MPR2. These simulations suggest that SF bile clearance along with the PBPK model can be used to quantify the effect of IRI on the activity of MRP2.Clinical Relevance- This study establishes the theory necessary to generate a model for predicting the degree of IRI during liver transplantation.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión
/
Trasplante de Hígado
Límite:
Animals
Idioma:
En
Revista:
Annu Int Conf IEEE Eng Med Biol Soc
Año:
2023
Tipo del documento:
Article