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

• Published in: Current drug metabolism Vol. 20; no. 7; p. 601
• Main Authors: Zhu, Linzhong, Zheng, Nan, Li, Xingang, Zhang, Xiaofeng
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2019
• Subjects: Animals; Female; Hepatic Artery - drug effects; Hepatic Artery - metabolism; Male; Quinazolines - administration & dosage; Quinazolines - pharmacokinetics; Swine; Thiophenes - administration & dosage; Thiophenes - pharmacokinetics; Raltitrexed; swine; peripheral vein; pharmacokinetics; hepatic arterial infusion; hepatic artery; two-compartmental model
• ISSN: 1875-5453
• DOI: 10.2174/1389200220666190618100847

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. 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. 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. 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.