|Title:||Local pelvic irradiation modulates Pharmacokinetics of 5-Fluorouracil in the plasma but not in the Lymphatic System||Authors:||Lee, Ya-yun
|Issue Date:||2015||Journal Volume:||15||Journal Issue:||1||Source:||BMC Cancer||Abstract:||
Background: 5-fluorouracil (5-FU) is employed to enhance radiotherapy (RT) effect. Here, we evaluated the influence of whole-pelvic irradiation on the pharmacokinetics (PK) of 5-FU in plasma and lymphatic system of rats as the experimental model. Methods: RT with 2Gy was delivered to the whole pelvis of Sprague-Dawley rats. 5-FU at 100mg/kg was intravenously infused 24hours after radiation. The pharmacokinetics of 5-FU in plasma and lymphatic system were calculated. Results: RT at 2Gy reduced the area under the plasma concentration vs. time curve and mean residence time of 5-FU by 21.5% and 31.5%, respectively compared with those of non-RT controls. By contrast, RT at 2Gy increased drug clearances of 5-FU by 28.2% when compared with those of non-RT controls. There was no significant difference in T1/2, Cmax and Vss in plasma between both groups. Intriguingly, 5-Fu could be detected in the lymphatic system. In addition, the AUC in 5-FU without and with RT was 3.3-fold and 4.9-fold greater for lymph than for plasma, respectively. Compared with the non-RT group, the RT group showed increase in distribution of 5-FU in the lymphatic system (p = 0.001). Conclusions: The local whole pelvic RT at 2Gy could modulate systemic PK of 5-FU in plasma of rats and intravenous 5-FU passing into the lymphatic system was proved. The metabolism of 5-FU might be modulated by RT but the distribution of 5-FU from blood circulation to the lymphatic system might not be changed. The RT-PK phenomena in plasma provide references for adjustment of drug administration. Chemotherapy drugs entering the lymphatic system is worthy of further investigation. ? 2015 Hsieh et al.; licensee BioMed Central.
|DOI:||10.1186/s12885-015-1344-4||metadata.dc.subject.other:||fluorouracil; fluorouracil; adult; animal experiment; area under the curve; Article; circulation; controlled study; drug blood level; drug clearance; drug distribution; drug half life; drug metabolism; lymphatic system; male; maximum plasma concentration; mean residence time; nonhuman; pelvis; plasma concentration-time curve; radiotherapy; rat; volume of distribution; animal; blood; drug effects; human; lymphatic system; multimodality cancer therapy; Neoplasms; pathology; radiation response; Animals; Combined Modality Therapy; Fluorouracil; Humans; Lymphatic System; Male; Neoplasms; Pelvis; Rats
|Appears in Collections:||物理治療學系所|
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