Cancer Chemotherapy and Pharmacology

, Volume 36, Issue 3, pp 211–216 | Cite as

Safety and efficacy of intraperitoneal injection of etoposide in oil suspension in mice with peritoneal carcinomatosis

  • Jung Soo Lee
  • Toshio Takahashi
  • Akeo Hagiwara
  • Chihiro Yoneyama
  • Michitoshi Itoh
  • Tsunetoshi Sasabe
  • Shozo Muranishi
  • Shigeru Tashima
Original Article Etoposide, Toxicity, Intraperitoneal Administration


We compared the safety and efficacy in mice with peritoneal carcinomatosis of two etoposide formulations: an aqueous solution (Etp-sol) and particles suspended in oil (the addition products of iodine and the ethyl esters of the fatty acids obtained from poppy-seed oil (Lipiodol) or sesame oil; Etp-oil). We also investigated tissue distribution of etoposide in rats treated with Etp-oil and Etp-sol. Etoposide was injected intraperitoneally at concentrations ranging from 52 to 392 mg/kg (increasing geometrically by a factor of 1.4). The 50% lethal dose (LD50), determined over a 2-week period of observation, was 135 mg/kg for Etp-oil and 108 mg/kg for Etp-sol. Autopsy findings included macroscopic intestinal bleeding, necrosis of the intestinal mucosa, and pulmonary congestion in mice from both treatment groups. In the efficacy trials. 106 P388 leukemia cells were transplanted into CDF1 male mice, and Etp-oil and Etp-sol were injected at doses of 20 mg/kg and 80 mg/kg. In the groups receiving the 20 mg/kg dose, 11 of 19 mice in the Etp-oil group survived to day 60 compared with 3 of 20 mice in the Etp-sol group. Toxicity-related deaths occurred in 1 of 20 mice treated with 80 mg/kg Etp-oil and in 8 of 20 mice treated with 80 mg/kg Etp-sol. No cancer-related deaths were associated with the 80 mg/kg dose in either treatment group. Our findings showed that the Etp-oil was associated with a lower toxicity and a higher efficacy than the Etp-sol. To evaluate tissue distribution, rats were injected intraperitoneally with 5 mg/kg body weight of Etp-sol or Etp-oil. The tissue distribution of etoposide was subsequently analyzed by high performance liquid chromatography. Compared with Etp-sol, Etp-oil delivered significantly greater amounts of etoposide and for a longer period to the omentum, taken as representative of the intraperitoneal tissue, and the etoposide concentration in blood plasma was increased more slowly and decreased more gradually.

Key words

Etoposide Toxicity Intraperitoneal administration 


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Jung Soo Lee
    • 1
  • Toshio Takahashi
    • 1
  • Akeo Hagiwara
    • 1
  • Chihiro Yoneyama
    • 1
  • Michitoshi Itoh
    • 1
  • Tsunetoshi Sasabe
    • 1
  • Shozo Muranishi
    • 2
  • Shigeru Tashima
    • 2
  1. 1.The First Department of SurgeryKyoto Prefectural University of MedicineKyotoJapan
  2. 2.Department of BiopharmacenticsKyoto College of PharmacyKyotoJapan

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