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


RESULTS
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).


CONCLUSIONS
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.
Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital, Taipei, Taiwan. chenciab@gmail.com.|Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan. chenciab@gmail.com.|Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. chenciab@gmail.com.
Chen-Hsi
CH
Hsieh
Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan. maylinghou@gmail.com.
Mei-Ling
ML
Hou
School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University, Taipei, Taiwan. liying@ntu.edu.tw.
Li-Ying
LY
Wang
Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan. will@ms1.mmh.org.tw.
Hung-Chi
HC
Tai
Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan. thtsai@ym.edu.tw.|Department of Education and Research, Taipei City Hospital, Taipei, Taiwan. thtsai@ym.edu.tw.
Tung-Hu
TH
Tsai
Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan. chenmdphd@gmail.com.|Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan. chenmdphd@gmail.com.|Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan. chenmdphd@gmail.com.
Yu-Jen
YJ
Chen
D000818:Animals; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008208:Lymphatic System / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010388:Pelvis / Q000473:pathology / Q000528:radiation effects*; D051381:Rats
D005472:Fluorouracil