Pharmacokinetic analysis of raltitrexed using different ways of drug delivery
10.3969/j.issn.1008-794X.2018.02.014
- VernacularTitle:雷替曲塞经不同给药方式的药动学分析
- Author:
Qiaosheng HUANG
1
,
2
;
Shaofeng CHEN
;
Zelong ZHONG
;
Weidong WANG
;
Tao ZHANG
;
Xiaoxia YU
;
Guocheng LI
;
Junyan WU
;
Linfeng XU
Author Information
1. 510000 广州 中山大学孙逸仙纪念医院介入科
2. 湖南湘潭市中心医院介入科
- Keywords:
rabbit liver cancer model,VX2;
raltitrexed;
LC-MS/MS;
hepatic arterial infusion;
pharmacokinetics
- From:
Journal of Interventional Radiology
2018;27(2):157-162
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the pharmacokinetics of raltitrexed using different ways of drug delivery, including femoral venous infusion, hepatic artery perfusion, hepatic artery injection of lipiodol suspension, hepatic artery perfusion followed by embolization with Gelfoam. Methods According to the administration way of raltitrexed, a total of 40 New Zealand rabbit models with VX2 liver tumor were randomly divided into group A (femoral venous perfusion), group B (hepatic arterial perfusion), group C (hepatic artery injection of lipiodol suspension), and group D(hepatic artery perfusion followed by embolization with Gelfoam). Drug concentration in plasma were determined by using LC-MS/MS method and the pharmacokinetic parameters were calculated. Results After administration of raltitrexed, the Tmax was 5 minutes in all 4 groups. In group A, B, C and D, the values were (5.88±1.39), (7.31±2.60), (9.86±5.10) and (7.19±2.27) respectively, with group C having the longest t1/2 value, which was significantly different with that of group A (P＜0.05); the (ng·ml-1·h-1) values were (2 056.40± 139.17), (1 389.21±180.28), (911.84±105.62) and (1 133.41±181.42)respectively, with the value of group A being obviously higher than that of group B, C and D (P＜0.05) and the value of group C being the lowest; the AUC0-t(ng· ml-1·h-1) values were (5 482.72±1 007.07), (4 156.99±1 475.77), (2 785.13±1 107.36) and (3 903.64±947.25) respectively, with the value of group A being remarkably higher than that of group B, C and D (P＜0.05) and the value of group C being the lowest. Conclusion Compared with the femoral vein infusion way, the ways of hepatic artery infusion, hepatic artery lipiodol suspension injection and hepatic artery perfusion followed by embolization with Gelfoam may promote more raltitrexed to deposit in the tumor area, thus, the curative effect is enhanced, the drug concentration in plasma is lowered and the side effects are alleviated.
