Limited sampling models for irinotecan pharmacokinetics

J. A. Sloan, P. Atherton Skaff, J. Reid, H. Pilot, C. Erlichman, L. Schaaf

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Irinotecan (CPT-11) AUC and its metabolites SN-38 glucuronide, SN-38 were modeled based on data from a Mayo Clinic phase I clinical trial involving 34 patients with advanced solid tumor malignancies on a q3 week dosing schedule. Multiple stepwise regression procedures were supplemented by all possible subsets regression analysis. A series of alternative clinically-based and empirically-derived limiting sampling models (LSM) will be presented with model validation assessment including jackknife and bootstrap simulation testing. A variety of LSM alternatives provided relatively equivalent accuracy in terms of predicting AUC. Given the wide variety of LSM alternatives, clinical considerations and patient burden become more important performance parameters than statistical considerations for the choice of time points in constructing LSMs. The best LSMs for CPT-11 AUC included concentrations at the end of the 90-minute infusion and four hours later with an option to include a blood draw at 6 hours post infusion. For SN-38 glucuronide and SN-38 AUC, optimal LSMs included the additional metabolite concentration at 48 hours post infusion. The LSMs are being taken forward into a phase II trial for gastric patients.

Original languageEnglish (US)
Number of pages1
JournalClinical pharmacology and therapeutics
Volume65
Issue number2
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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