Local pelvic irradiation modulates Pharmacokinetics of 5-Fluorouracil in the plasma but not in the Lymphatic System

• Published in: BMC cancer Vol. 15; no. 1; p. 316
• Main Authors: Hsieh, Chen-Hsi, Hou, Mei-Ling, Wang, Li-Ying, Tai, Hung-Chi, Tsai, Tung-Hu, Chen, Yu-Jen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.04.2015; BioMed Central
• Subjects: Analysis; Animals; Cancer; Care and treatment; Chemotherapy; Colorectal cancer; Combined Modality Therapy; Comparative analysis; Diagnosis; Fluorouracil; Fluorouracil - administration & dosage; Fluorouracil - blood; Fluorouracil - pharmacokinetics; Health aspects; Humans; Lymphatic System - drug effects; Lymphatic System - pathology; Lymphatic System - radiation effects; Male; Neoplasms - blood; Neoplasms - drug therapy; Neoplasms - pathology; Pelvis - pathology; Pelvis - radiation effects; Radiation; Rats
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-015-1344-4

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. RT with 2 Gy was delivered to the whole pelvis of Sprague-Dawley rats. 5-FU at 100 mg/kg was intravenously infused 24 hours after radiation. The pharmacokinetics of 5-FU in plasma and lymphatic system were calculated. RT at 2 Gy 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 2 Gy 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). The local whole pelvic RT at 2 Gy 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.