A pharmacokinetic and pharmacodynamic analysis of CPT-11 and its active metabolite SN-38

Jpn J Cancer Res. 1995 Jan;86(1):101-10. doi: 10.1111/j.1349-7006.1995.tb02994.x.


In the present study, an attempt was made to determine the precise pharmacokinetics of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). The relationship between pharmacokinetic parameters and pharmacodynamic effects was also investigated to elucidate the cause of interpatient variation in side effects. Thirty-six patients entered the study. CPT-11, 100 mg/m2, was administered by IV infusion over 90 min weekly for four consecutive weeks. The major dose-limiting toxicities were leukopenia and diarrhea. There was a positive correlation between the area under the concentration-time curve (AUC) of CPT-11 and percent decrease of WBC (r = 0.559). On the other hand, episodes of diarrhea had a better correlation with the AUC of SN-38 (r = 0.606) than that of CPT-11 (r = 0.408). Multivariate analysis revealed that the AUC of SN-38, AUC of CPT-11 and indocyanine green retention test were significant variables for the incidence of diarrhea and that both performance status and AUC of CPT-11 were significant variables for percent decrease of WBC. The large interpatient variability of the degree of leukopenia and diarrhea is due to a great plasma pharmacokinetic variation in CPT-11 or SN-38. The AUCs of CPT-11 and SN-38 obtained from the first administration of CPT-11 correlate with toxicities, but it is impossible to predict severe side effects before the administration of CPT-11 at the present time.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic*
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacokinetics
  • Camptothecin / pharmacology
  • Diarrhea / chemically induced
  • Female
  • Humans
  • Irinotecan
  • Japan
  • Kinetics
  • Leukopenia / chemically induced
  • Male
  • Middle Aged
  • Neoplasms / metabolism*
  • Prospective Studies


  • Antineoplastic Agents, Phytogenic
  • Irinotecan
  • Camptothecin