Open AccessIn vitro conversion of irinotecan to SN‐38 in human plasma
Author(s) -
Shingyoji Masato,
Takiguchi Yuichi,
WatanabeUruma Reiko,
AsakaAmano Yoshiko,
Matsubara Hiroshi,
Kurosu Katsushi,
Kasahara Yasunori,
Tanabe Nobuhiro,
Tatsumi Koichiro,
Kuriyama Takayuki
Publication year - 2004
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2004.tb03245.x
Subject(s) - irinotecan , in vivo , sn 38 , active metabolite , ex vivo , in vitro , metabolite , coefficient of variation , chemistry , pharmacokinetics , medicine , cancer , high performance liquid chromatography , enzyme , human plasma , endocrinology , pharmacology , chromatography , biology , biochemistry , colorectal cancer , microbiology and biotechnology
Irinotecan is an active cytotoxic agent for various cancers, and is converted to SN‐38, its most active metabolite, by carboxy‐lesterase 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 μ M irinotecan to plasma, time courses of SN‐38 concentration, measured by high‐performance liquid chromatog‐raphy (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.