Title Page
Abstract
Contents
PRECEDING STUDY 11
INTRODUCTION 32
METHODS 34
RESULTS 38
DISCUSSION 51
Bibliography 56
국문 초록 62
Table 1. Patient characteristics of the preceding study 20
Table 2. Sensitivity analysis result for T₅₀ 21
Table 3. Covariate screening result 22
Table 4. Final population pharmacokinetic model parameters 24
Table 5. Patient characteristics of the main study 41
Table 6. AT-III plasma activity levels and target attainment rates of patients after ICU admission 43
Figure 1. Distribution of plasma antithrombin III levels in the liver transplantation patients during postoperative days 25
Figure 2. Distribution of plasma antithrombin III levels in the liver transplantation patients during dosing intervals 26
Figure 3. Final model scheme for the population pharmacokinetic analysis of AT-III 27
Figure 4. Goodness of fit plots for the final model 28
Figure 5. Visual predictive check plot for model development dataset (a) and external validation dataset (b) 29
Figure 6. Prediction errors (a) and absolute prediction errors (b) of the final population pharmacokinetic model when applied to external validation dataset 30
Figure 7. Simulated plasma AT-III activity levels according to various dosing scenarios 31
Figure 8. Simulation of the intermittent infusion regimen 44
Figure 9. Schematic diagram of the study protocol 45
Figure 10. Consolidated Standards of Reporting Trials (CONSORT) flow diagram of the study 46
Figure 11. Observed plasma AT-III activity levels during 84 hours after liver transplantation 47
Figure 12. Time required for plasma AT-III activity level to reach target range after liver transplantation 48
Figure 13. Proportion of total plasma AT-III activity levels within target AT-III activity range 49
Figure 14. Mean (bold line) and individual (hairline) values of prothrombin time, hemoglobin, platelet counts, and serum albumin during the study period 50