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Hepatic Artery and Peripheral Vein Pharmacokinetics of Raltitrexed in Swine After the Administration of a Hepatic Arterial Infusion

[ Vol. 20 , Issue. 7 ]

Author(s):

Linzhong Zhu, Nan Zheng*, Xingang Li and Xiaofeng Zhang   Pages 601 - 608 ( 8 )

Abstract:


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.

Keywords:

Raltitrexed, hepatic arterial infusion, hepatic artery, peripheral vein, pharmacokinetics, two-compartmental model, swine.

Affiliation:

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Interventional Therapy, Peking University Cancer Hospital and Institute, Beijing 100142, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), National Drug Clinical Trial Center, Peking University Cancer Hospital and Institute, Beijing 100142, Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, Department of Radiology, Beijing Obstetrics and Gynecology Hospital, Beijing 100006

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