title: Pelvic irradiation modulates the pharmacokinetics of cisplatin in the plasma and lymphatic system.
abstract: BACKGROUND
  Cisplatin (CDDP) is employed to enhance radiotherapy's (RT) effect for various cancers. However, the effects of local RT on chemotherapeutics in the plasma and lymphatic system remain unclear. Here, we evaluated the influence of pelvic irradiation on the pharmacokinetics (PK) of CDDP using rats as an experimental model.
  
  
  METHODS
  RT with 2 Gy and 0.5 Gy were delivered to the whole pelvis of Sprague-Dawley rats. CDDP at 5 mg/kg and 10 mg/kg was intravenously infused 24 hours after radiation for the plasma and lymphatic system, respectively. The pharmacokinetics of CDDP in the plasma and lymphatic system were calculated.
  
  
  RESULTS
  Compared with sham-irradiated controls, the whole pelvic irradiation increased the area under the concentration versus time curve (AUC) of CDDP (5 mg/kg) in the plasma by 80% at 0.5 Gy and 87% at 2 Gy, respectively. In contrast, the AUC of CDDP decreased in bile by 13% at both dose levels. Intriguingly, RT could also increase the AUC of CDDP (10 mg/kg) in the lymphatic fluid by 87% at 2 Gy. In addition, the AUC in CDDP without and with RT was 2.8-fold and 3.4-fold greater for the lymph system than for the plasma, respectively.
  
  
  CONCLUSIONS
  A local pelvic RT could modulate the systemic PK of CDDP in both the plasma and lymphatic fluids of the rats. The RT-PK phenomena are worth further investigation.
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University Taipei, Taiwan ; Department of Education and Research, Taipei City Hospital Taipei, Taiwan.
authors.forename: Tung-Hu
authors.initials: TH
authors.lastname: Tsai
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University Taipei, Taiwan ; Department of Radiation Oncology, Mackay Memorial Hospital Taipei, Taiwan ; Department of Medical Research, Mackay Memorial Hospital Taipei, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University Taipei, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Hou
authors.affiliation: School and Graduate Institute of Physical Therapy, College of Medicine, National Taiwan University Taipei, Taiwan.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Mackay Memorial Hospital Taipei, Taiwan.
authors.forename: Hung-Chi
authors.initials: HC
authors.lastname: Tai
authors.affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University Taipei, Taiwan ; Department of Medicine, School of Medicine, National Yang-Ming University Taipei, Taiwan ; Division of Radiation Oncology, Department of Radiology, Far Eastern Memorial Hospital Taipei, Taiwan.
authors.forename: Chen-Hsi
authors.initials: CH
authors.lastname: Hsieh
keywords: Cisplatin (CDDP); RT-PK; concurrent chemoradiation therapy (CCRT); pharmacokinetics; radiosensitivity