Background: Hepatic Arterial Infusion (HAI) with raltitrexed has become an effective treatment for hepatocellular
cancer and colorectal cancer liver metastases. However, traditional Body Surface Area (BSA)-based dosing
is unsafe or ineffective, and a more accurate model-based approach is required.
Methods: In this study, domestic swine were given 1 mg or 4 mg raltitrexed administered by an HAI with infusion
times of 30, 60 and 120 min. Hepatic Artery (HA) and Peripheral Vein (PV) samples were collected, and a twocompartment
model with an elimination pathway was established to describe the in vivo behavior of raltitrexed.
Results: The clearance was 0.27 L/min, and the volumes of distribution were 0.35 and 6.65 L for the HA and PV
compartments, respectively. The goodness-of-fit plots and visual predictive checks suggested that the proposed
pharmacokinetic model agreed well with the observations.
Conclusion: The pharmacokinetic model could be helpful in quantitatively describing the detailed processes of raltitrexed
activity administered by HAI and determining an appropriate dosing regimen for preclinical and clinical