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Current Drug Metabolism

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ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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Research Article

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

Author(s): Linzhong Zhu, Nan Zheng*, Xingang Li and Xiaofeng Zhang

Volume 20, Issue 7, 2019

Page: [601 - 608] Pages: 8

DOI: 10.2174/1389200220666190618100847

Price: $65

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.

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