Current drug metabolism · 2019
Hepatic Artery and Peripheral Vein Pharmacokinetics of Raltitrexed in Swine After the Administration of a Hepatic Arterial Infusion.
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Zhu Linzhong, Zheng Nan, Li Xingang, Zhang Xiaofeng
Аннотация
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 studies.
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 studies.