Japanese Journal of Clinical Oncology 33:377-381 (2003)
© 2003 Foundation for Promotion of Cancer Research
Pharmacokinetics of 5-Fluorouracil Following Hepatic Intra-arterial Infusion in a VX2 Hepatic Metastasis Model
1 Department of Surgery and 2 Department of Radiology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan
Background: Hepatic intra-arterial infusion chemotherapy of 5-fluorouracil (5-FU) or fluorodeoxyuridine (FUDR) has been a treatment option for liver metastasis from colorectal cancer. However, an optimal administration schedule of 5-FU is still controversial. This study was conducted to evaluate a suitable schedule from the viewpoint of 5-FU metabolites and related enzymes.
Methods: 5-FU was infused into the hepatic artery of rabbits having hepatic deposits of VX2 tumor cells in a daily dose of 1, 4, or 8 mg/kg using various schedules. 5-FU, Thymidylate synthase (TS), TS inhibition rate (TSIR), and the amount of fluoro-RNA (F-RNA) were measured.
Results: A high concentration of 5-FU was detected in the tumors of the group that was administered a dose of 8 mg/kg. TSIR in the tumor was about two-fold higher in the rabbits that were administered a total dose of 8 mg/kg than in those that were administered doses of 4 mg/kg or less. F-RNA, ranging from 27 to 36 ng/mg RNA, was detected in the tumor of the rabbits that were administered a total dose of 8 mg/kg. No difference was observed between the short period and the continuous administration schedules of rabbits that were administered a dose of 8 mg/kg of 5-FU. However, DNA synthesis inhibition in normal hepatic tissue was more dependent on the administration schedule than on the total dose of 5-FU because TSIR was significantly higher with shorter periods of drug administration.
Conclusion: Intermittent bolus administration of large doses of 5-FU might cause more severe hepatic impairment than continuous administration. These results suggest that hepatic intra-arterial infusion of 5-FU should be administered continuously for liver metastasis, although further experiments including a longer administration period of 5-FU are required.
+ For reprints and all correspondence: Sotaro Sadahiro, Department of Surgery, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan. E-mail: sadahiro{at}is.icc.u-tokai.ac.jp
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Liu, H. Sun, W. Y. Valji, and K. S. Pang Transporters, enzymes, and enalapril removal in a rat (CC531-induced) liver metastatic model Am J Physiol Gastrointest Liver Physiol, November 1, 2007; 293(5): G1078 - G1088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hong, A. Khwaja, E. Liapi, M. S. Torbenson, C. S. Georgiades, and J.-F. H. Geschwind New Intra-arterial Drug Delivery System for the Treatment of Liver Cancer: Preclinical Assessment in a Rabbit Model of Liver Cancer Clin. Cancer Res., April 15, 2006; 12(8): 2563 - 2567. [Abstract] [Full Text] [PDF]
|
|