Pharmacological correlation between total drug concentration and lactones of CPT-11 and SN-38 in patients treated with CPT-11

Jpn J Cancer Res. 1995 Jan;86(1):111-6. doi: 10.1111/j.1349-7006.1995.tb02995.x.


The pharmacokinetics of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), were examined to establish the pharmacokinetic variability of the active lactones of CPT-11 and SN-38 in comparison with that of the total (lactone and carboxylates) plasma CPT-11 and SN-38. Twelve patients with malignancies were entered in the study. All received 100 mg/m2 of CPT-11 by intravenous drip infusion over 90 min. Blood was sampled at 10 time points in heparin-containing syringes. Analysis by high-performance liquid chromatography showed that the ratio of CPT-11 lactone to total CPT-11 concentration was highest (66%) just after the end of infusion and gradually decreased to 30% at 24 h. Almost 70% of SN-38 lactone was detected after the end of infusion and this decreased to 50% within 24 h. The standard errors of percent lactone of CPT-11 of SN-38 to total drug concentration at each sampling point were less than 12%. The area under the concentration-time curve (AUC) of total CPT-11 and that of total SN-38 were significantly correlated with the AUCs of the lactone CPT-11 and those of lactone SN-38, respectively. We conclude that, for practical purposes, monitoring of total CPT-11 and SN-38 has essentially the same clinical significance as monitoring of lactone CPT-11 and SN-38.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / blood
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / blood
  • Camptothecin / pharmacokinetics
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Irinotecan
  • Kinetics
  • Lactones / blood
  • Lactones / pharmacokinetics*
  • Male
  • Middle Aged
  • Neoplasms / blood*
  • Prospective Studies


  • Antineoplastic Agents, Phytogenic
  • Lactones
  • Irinotecan
  • Camptothecin