EFFECTS OF LEVOFOLINATE CALCIUM ON SUBACUTE INTRAVENOUS TOXICITY OF 5-FLUOROURACIL IN RATS
書誌事項
- タイトル別名
-
- Effects of levofolinate calcium on suba
この論文をさがす
抄録
To clarify whether levofolinate calcium (1-LV) enhances 5-fluorouracil (5-FU) toxicity, a 4-week toxicity study of 5-FU (10 mg/kg/day) in combination with 1-LV (6, 20 or 60 mg/kg/day) was conducted in rats. In the 5-FU alone group, a decrease in body weight gain, food consumption, RBC parameter and WBC counts were detected. Histopathologically, lymphoid depletion of lymphatic organs, hematopoiesis enhancement of the spleen and myelosuppression were observed. In the group for which 5-FU was combined with 1-LV, the RBC counts decreased, extramedullary hematopoiesis increased and the suppression of lymphatic organs was enhanced. Changes in the lymphatic organs were observed at 20 mg/kg/day of 1-LV and above. In monitoring of blood drug concentrations of 1-LV, 5-methyl tetrahydrofolic acid, a metabolite of 1-LV, and 5-FU after the 1st and 14th dosings, there was no apparent difference between 5-FU alone and 5-FU combined with 1-LV in Cmax and AUC0-∞. The potentiation induced by 1-LV in the toxicity of 5-FU appeared to be mainly immuno-suppression and myelosuppression, which were related to the anti-tumor activity of 5-FU. Plasma concentrations of 5-FU and 1-LV in this study overwhelmed the concentrations that enhancement of thymidylate synthetase (TS) inhibition due to 5-FU was observed by addition of 1-LV in vitro. Therefore toxic potentiation of 5-FU due to simultaneous 1-LV dosing is presumed to be concerned with an increased ternary complex (FdUMP-TS-5, 10-methylenetetrahydrofolate) formation and a greater extent of TS inhibition.
収録刊行物
-
- The Journal of Toxicological Sciences
-
The Journal of Toxicological Sciences 23 (SupplementI), 11-29, 1998
一般社団法人 日本毒性学会
- Tweet
キーワード
詳細情報 詳細情報について
-
- CRID
- 1390001204903071616
-
- NII論文ID
- 110001806147
-
- NII書誌ID
- AN00002808
-
- ISSN
- 18803989
- 03881350
-
- NDL書誌ID
- 4471839
-
- 本文言語コード
- en
-
- データソース種別
-
- JaLC
- NDL
- Crossref
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可