A limited sampling strategy to estimate the pharmacokinetic parameters of irinotecan and its active metabolite, SN-38, in patients with metastatic digestive cancer receiving the FOLFIRI regimen.
In this study we propose for the first time a limited sampling strategy to estimate the individual pharmacokinetic parameters of both irinotecan and SN-38 in patients treated with the irinotecan plus 5-fluorouracil (FOLFIRI) regimen. The pharmacokinetics of irinotecan and SN-38 were studied in 74 patients with advanced inoperable digestive cancer. Plasma concentrations were taken during and up to the 42 h following a 90-min infusion of irinotecan (180-225 mg/m(2)). Data splitting was used to create model-building and validation data sets, and data were analysed with the NONMEM program. The disposition of SN-38 was dependent on the disposition of irinotecan. The estimated pharmacokinetic parameters of irinotecan [terminal half-life (t(1/2)), 11.5 h; total clearance (CL), 25.0 l h(-1); area under curve (AUC), 14.9 mg x h l(-1)] and SN-38 (terminal t(1/2), 32.2 h; AUC, 0.42 mg x h l(-1)) were similar to those determined in other studies. The protocol involving two sampling times, at 1 and 24 h following the beginning of the infusion, allowed for a precise and accurate determination of the individual pharmacokinetic parameters of the two drugs. The limited sampling strategy developed in this study ought to facilitate future studies on the pharmacology and toxicity of irinotecan-based therapy.
Poujol
Sylvain
S
Oncopharmacology Department, Pharmacy Service, Faculty of Pharmacy, University Montpellier I, 34093 Montpellier Cedex 5, France.
Pinguet
Frederic
F
Ychou
Marc
M
Abderrahim
Anissa Gauthey
AG
Duffour
Jacqueline
J
Bressolle
Françoise M M
FM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001499:Bayes Theorem; D001830:Body Surface Area; D001835:Body Weight; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004067:Digestive System Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009362:Neoplasm Metastasis; D015203:Reproducibility of Results
D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin