In vitro partition of irinotecan (CPT-11) in human volunteer blood: the influence of concentration, gender and smoking

Anticancer Drugs. 2005 Sep;16(8):893-5. doi: 10.1097/


We have performed in vitro incubations of blood from male and female volunteers, smokers and non-smokers, with irinotecan at a gradient of different concentrations in order to investigate changes of partition between red blood cells (RBCs), total plasma and the free fraction. Since irinotecan (CPT-11) is not metabolized in vitro, there is no data available on its active metabolite SN-38. After extraction and sample pre-treatment, a validated high-performance liquid chromatography method followed by fluorescence detection was used to determine the concentration of the drug in the different blood constituents. The partition ratio [the concentration in the erythrocytes divided by the concentration in plasma (E/P)] was calculated. The partition ratio of CPT-11 varied from 0.7 to 2.8, reflecting its relatively high affinity for the erythrocyte, probably because of its only moderate plasma protein binding (65%). The partition ratios increased significantly with higher whole-blood concentrations, favoring uptake in the erythrocytes when plasma protein binding is saturated. No gender difference was detected, but we found relatively more CPT-11 in the erythrocytes of non-smokers compared to smokers. The incorporation of drugs into the RBC pool may be important for transportation to tumor tissue and efficacy. Smoking can have a significant influence on drug partition in the blood.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents, Phytogenic / blood*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / blood
  • Camptothecin / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Erythrocytes / metabolism*
  • Female
  • Humans
  • In Vitro Techniques
  • Irinotecan
  • Male
  • Sex Distribution
  • Smoking / adverse effects*
  • Spectrometry, Fluorescence
  • Topoisomerase I Inhibitors


  • Antineoplastic Agents, Phytogenic
  • Topoisomerase I Inhibitors
  • Irinotecan
  • Camptothecin