Pharmacokinetics of human antithrombin III concentrate in the immediate postoperative period after liver transplantation.

Abstract

Antithrombin III (AT-III) concentrates have been used to prevent critical thrombosis in the immediate post-liver transplantation period without clear evidence regarding the optimal dose or administration scheme. The relationship between the AT-III dosage and the plasma activity levels during the period was evaluated in this study. The plasma AT-III activity levels and clinical data obtained from patients who received liver transplantation from January 2017 to September 2018 were retrospectively analysed. A population pharmacokinetic (PK) model was developed using nonlinear mixed-effects method and externally validated thereafter. Several dosing scenarios were simulated to maintain the plasma AT-III activity level within the normal range using the developed PK model to search for an optimal AT-III dosing regimen. The plasma AT-III activity levels were best described by a single compartment model with first order elimination kinetics. The recovery of endogenous AT-III level during the postoperative days was modelled using an Emax model. The typical values (95% confidence interval) of volume of distribution and clearance were 3.86 (3.40-4.32) L, and 0.129 (0.111-0.147) L h-1 , respectively. Serum albumin and body weight had significant effect on clearance and were included in the model. External validation of the proposed model demonstrated adequate prediction performance. Furthermore, simulation of previously suggested or modified dosing scenarios showed successful maintenance of AT-III activity level within the normal range. A population PK model of AT-III concentrate was developed using data from liver recipients. Dosing scenarios simulated in our study may help establish a practical guide for AT-III concentrate titration after liver transplantation.