Pharmacokinetics of consecutive intra-arterial and intravenous infusion of 5-fluorouracil and 4′-Otetrahydropyr-anayladriamycin
10.3781/j.issn.1000-7431.2008.06.006
- Author:
Yu-Qin ZHANG
1
Author Information
1. Department of Gynecology
- Publication Type:Journal Article
- Keywords:
Animals experimentation;
Antineoplastic combined chermotherapy protocols;
Injection, intravenous;
Injections ,Intra-arterial;
Phrmacokinetics
- From:
Tumor
2008;28(6):480-484
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To study the pharmacokinetics and factors influencing consecutive internal iliac arterial and intravenous infusion of 5-fluorouracil 5-FU and 4′ -O-tetrahydropyranyladriamycin (THP) and provide the experimental evidence to optimize intra-artery chemotherapy for pelvic malignant tumor. Methods:Mature female New Zealand rabbits were divided randomly into two groups. One group was consecutively infused by 5-FU and THP via internal iliac artery for 6 h. The other group was consecutively infused by 5-FU and THP via ear vein. The blood samples and the uterus tissue specimens were collected at various time points during the infusion period. At the end of infusion, the rabbits were sacrificed via intravenous air embolism and the heart, lung, and the node-rich pelvic adipose tissues were collected. The drug concentrations in plasma and tissue specimens were determined by high performance liquid chromatography methods. Results: The peak plasma concentration and AUC (area under curve) of intra-arterial infusion of 5-FU were a little lower than those via intravenous infusion. The peak concentration of intra-arterial infusion of 5-FU were 2-3 fold increased in uterus tissues and 5-fold increased in pelvic lymph node and adjacent tissues compared with those via intravenous infusion. The peak plasma concentration and AUC of intra-arterial infusion of THP were lower than those via intravenous infusion. The peak concentration and AUC of intra-arterial infusion of THP were not significantly different in uterus tissues between the two infusion forms. The peak concentration of THP was decreased by 50% in heart and lung tissues but increased to 5-fold in pelvic peripheral lymph node tissues by intra-arterial infusion than those by intravenous infusion. The serum to tissue vein distribution ratio of THP was several hundred times. Conclusions: Consecutive intra-arterial infusion of 5-FU and THP had some advantages compared with continuous intravenous infusion at different degrees. These advantages depended on the drugs' pharmacological properties.
