title: Pharmacokinetic assessment of irinotecan, SN-38, and SN-38-glucuronide: a substudy of the FIRIS study.
abstract: BACKGROUND
  We evaluated the pharmacokinetics of irinotecan (CPT-11) and its metabolites in patients with metastatic colorectal cancer receiving the combination of CPT-11/S-1 (IRIS) or 5-fluorouracil (5-FU)/l-leucovorin (LV)/CPT-11 (FOLFIRI) regimens in the FIRIS trial.
  
  
  METHODS
  Serum CPT-11, SN-38 (an active metabolite of CPT-11), and SN-38-glucuronide concentrations were compared between the IRIS and FOLFIRI regimens, and between days 1 and 15 of administration. Correlations between pharmacokinetic data and incidence of neutropenia and diarrhea were also assessed.
  
  
  RESULTS
  There were no significant differences in the pharmacokinetics of CPT-11 or its metabolites between days 1 and 15. SN-38 concentrations were correlated with the occurrence of neutropenia, which was significantly more frequent in the FOLFIRI group than in the IRIS group.
  
  
  CONCLUSIONS
  No alterations in CPT-11 pharmacokinetics after repeated IRIS or FOLFIRI administration were observed. Neutropenia was more frequent in the FOLFIRI group than in the IRIS group because exposure to SN-38 was greater in the former group.
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. taroh@cfs.med.osaka-u.ac.jp.
authors.forename: Taroh
authors.initials: T
authors.lastname: Satoh
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yasui
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sameshima
authors.forename: Kensei
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D020719:Glucuronides / Q000493:pharmacokinetics*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged
chemical_list: C441475:7-ethyl-10-hydroxycamptothecin glucuronide; D000972:Antineoplastic Agents, Phytogenic; D020719:Glucuronides; D000077146:Irinotecan; D002166:Camptothecin
keywords: FIRIS; IRIS; Irinotecan; S-1; colorectal cancer