Pharmacokinetics of irinotecan and its metabolites SN-38 and APC in children with recurrent solid tumors after protracted low-dose irinotecan

Margaret K. Ma, William C. Zamboni, Kristine M. Radomski, Wayne L. Furman, Victor M. Santana, Peter J. Houghton, Suzan K. Hanna, Audrey K. Smith, Clinton F. Stewart

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Irinotecan (IRN), a topoisomerase I interactive agent, has significant antitumor activity in early Phase I studies in children with recurrent solid tumors. However, the disposition of IRN and its metabolites, SN-38 and APC, in children has not been reported. Children with solid tumors refractory to conventional therapy received IRN by a 1-h i.v. infusion at either 20, 24, or 29 mg/m2 daily for 5 consecutive days for 2 weeks. Serial blood samples were collected after doses 1 and 10 of the first course. IRN, SN-38, and APC lactone concentrations were determined by an isocratic high-performance liquid chromatography assay. A linear four-compartment model was fit simultaneously to the IRN, SN-38, and APC plasma concentration versus time data. Systemic clearance rate for IRN was 58.7 ± 18.8 liters/h/m2 (mean ± SD). The mean ± SD ng/ml·h single-day lactone SN-38 area under the concentration-time curve (AUC(0→6)) was 90.9 ± 96.4, 103.7 ± 62.4, and 95.3 ± 63.9 at IRN doses of 20, 24, and 29 mg/m2, respectively. The relative extent of IRN conversion to SN-38 and metabolism to APC measured after dose 1 were 0.49 ± 0.33 and 0.29 ± 0.17 (mean ± SD). No statistically significant intrapatient difference was noted for SN-38 area under the concentration-time curve. Large interpatient variability in IRN and metabolite disposition was observed. The relative extent of conversion and the SN-38 systemic exposure achieved with this protracted schedule of administration were much greater than reported in adults or children receiving larger intermittent doses.

Original languageEnglish (US)
Pages (from-to)813-819
Number of pages7
JournalClinical Cancer Research
Issue number3
StatePublished - Mar 2000
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Pharmacokinetics of irinotecan and its metabolites SN-38 and APC in children with recurrent solid tumors after protracted low-dose irinotecan'. Together they form a unique fingerprint.

Cite this