title: Comparisons of the pharmacokinetics and the leukopenia and thrombocytopenia grade after administration of irinotecan and 5-fluorouracil in combination to rats.
abstract: BACKGROUND
  Irinotecan (CPT-11) has been used recently for the treatment of several cancers in combination with 5-fluorouracil (5-FU). Preliminary data on this combination therapy in humans demonstrated no drug interactions between CPT-11 (or its metabolite, SN-38) and 5-FU however, because there is so little information on the combination, the possibility for an interaction still exists.
  
  
  METHODS
  CPT-11 and 5-FU were injected intravenously into rats and the pharmacokinetics of CPT-11 and SN-38 and alternations in blood cell count were investigated.
  
  
  RESULTS
  In the group of rats administered 5-FU prior to CPT-11, the area under the concentration-time curve (AUC) of CPT-11 was approximately eight-fold larger compared with the group administered CPT-11 prior to 5-FU. On the other hand, the grade of leukocytopenia or thrombocytopenia was not significantly different among the two groups.
  
  
  CONCLUSIONS
  In rats, the conversion of CPT-11 into SN-38 is possibly delayed by prior administration of 5-FU.
authors.affiliation: Third Department of Internal Medicine, Yokohama City University, School of Medicine 3-9, Fukuura Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Umezawa
authors.forename: T
authors.initials: T
authors.lastname: Kiba
authors.forename: K
authors.initials: K
authors.lastname: Numata
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Nakaoka
authors.forename: S
authors.initials: S
authors.lastname: Shintani
authors.forename: H
authors.initials: H
authors.lastname: Sekihara
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004912:Erythrocytes / Q000187:drug effects; D005472:Fluorouracil / Q000009:adverse effects / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D000077146:Irinotecan; D007970:Leukopenia / Q000139:chemically induced*; D008297:Male; D051381:Rats; D013921:Thrombocytopenia / Q000139:chemically induced*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin