title: In vitro conversion of irinotecan to SN-38 in human plasma.
abstract: Irinotecan is an active cytotoxic agent for various cancers, and is converted to SN-38, its most active metabolite, by carboxylesterase converting enzyme (CCE) in vivo. Although the primary metabolic site is in the liver, ex vivo studies have proven that irinotecan is also converted to SN-38 in intestines, plasma and tumor tissues. The present study attempted to elucidate the in vitro conversion efficiency in human plasma, and to examine possible inter-individual variability and its clinical significance. Plasma samples were taken from 57 patients with lung cancer, 3 patients with benign pulmonary diseases and 9 healthy volunteers. After addition of 157 mM irinotecan to plasma, time courses of SN-38 concentration, measured by high-performance liquid chromatography (HPLC), were investigated. All subjects showed linear increase in SN-38 concentration during the first 60-min period, followed by a plateau. Mean and standard deviation of the conversion rate in the first 60 min were 515.9 +/- 50.1 pmol/ml/h (n = 69), with a coefficient of variation of 0.097. Although most of the subjects showed comparable conversion rates, 3 subjects had significantly higher conversion rates. In conclusion, the results of this study suggest that the enzyme activity of CCE in human plasma may show inter-individual variability.
authors.affiliation: Department of Respirology (B2), Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670.
authors.forename: Masato
authors.initials: M
authors.lastname: Shingyoji
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takiguchi
authors.forename: Reiko
authors.initials: R
authors.lastname: Watanabe-Uruma
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Asaka-Amano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsubara
authors.forename: Katsushi
authors.initials: K
authors.lastname: Kurosu
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kasahara
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tanabe
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kuriyama
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000378:metabolism*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin