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The influence of different interventional injection routes of raltitrexed on the liver function, histology and pharmacokinetics in experimental rabbits / 介入放射学杂志
Journal of Interventional Radiology ; (12): 247-251, 2018.
Article in Chinese | WPRIM | ID: wpr-694245
ABSTRACT
Objective To assess the influence of different interventional injection routes of raltitrexed on the liver function, histology and pharmacokinetics in experimental rabbits, and to discuss the feasibility, safety and advantages of local application of raltitrexed. Methods A total of 25 New Zealand white rabbits were randomly and equally divided into 5 groups with 5 rabbits in each group group A (using peripheral intravenous injection), group B (employing hepatic arterial infusion), group C (adopting hepatic artery embolization with Lipiodol), group D (hepatic artery embolization with gelfoam particles), and group E (direct puncture of liver and injection). Clinical equivalent dose (0. 17 mg/kg) raltitrexed injection was given to each experimental rabbit. At 5, 15, 30, 60, 120 and 180 min after the treatment, venous blood sample was collected for pharmacokinetic analysis. At 6 h and one week after administration of drug, liver functions were tested, and histological specimens of liver tissues were made at the same time. Results The peripheral blood drug concentrations at 5 and 60 min in group A were 0. 91 μg/mL and 0 μg/mL respectively, at 5 and 180 min in group B were 1. 73 μg/mL and 0. 37 μg/mL respectively, at 5 and 180 min in group C were 0. 82 μg/mL and 0. 08 μg/mL respectively, at 5 and 180 min in group D were 0. 94 μg/mL and 0. 08 μg/mL, and at 5 and 60 min in group E were 0. 39 μg/mL and 0. 13 μg/mL respectively. Six hours after administration of drug, the serum levels of AST, ALT in group C, group D and group E were significantly increased (P<0. 0l), which returned to normal levels in one week after the treatment. The severity of liver tissue degeneration and necrosis detected in each group varied, in a severity - decreasing order, from group E, group C, group D, group B and group A. In group E, the surrounding normal liver tissue had no obvious necrosis. Conclusion The rabbit' s liver has no significant first pass elimination effect to raltitrexed. The equivalent dose of raltitrexed administered through the hepatic artery can cause obvious hepatocellular injury. Direct puncture and injection produce limited liver injury. Clinically, the dose of raltitrexed can be adjusted based on the degree of super selective catheterization condition and tumor size. (J Intervent Radiol, 2018, 27247-251)

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Journal of Interventional Radiology Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Journal of Interventional Radiology Year: 2018 Type: Article