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Irinotecan (CPT-11), a prodrug for treating metastatic colorectal cancer, is a topoisomerase I inhibitor for LoVo cells and HT-29 cells with IC50 of 15.8 μM and 5.17 μM, respectively [1].In vivo, Irinotecan is converted to SN-38, its most active metabolite, by carboxylesterase converting enzyme (CCE) [2].

In vitro: Irinotecan induced similar amounts of cleavable complexes in LoVocells and HT-29 cell lines with the IC50 of 15.8 μM and 5.17 μM, respectively [1].After addition of 157 mM irinotecan to plasma, SN-38 concentration showed linear increase during the first 60-min period, followed by a plateau.In the first 60 min, mean and standard deviation of the conversion rate were 515.9 ± 50.1 pmol/ml/h (n = 69), with a coefficient of variation of 0.097 [2]. Irinotecan (CPT-11) was significantly more active in SCLC than in NSCLCcelllines (P = 0.0036). CE activity appeared to be associated with higher sensitivity to CPT-11 in human lung cancercelllines and may partly explain the difference in the in vitro sensitivity to CPT-11 between SCLC and NSCLCcells [3].In vitro, the sensitivity to CPT-11 and SN-38 was highest in LS174T and COLO 320cells, intermediate in SW1398cellsand lowest in COLO 205 and WiDr cells. The activity of SN-38 was 130 to 570 times than CPT-11[4].

In vivo: In COLO 320 xenografts, Irinotecan induced a maximum growth inhibition of 92% [4].A single dose of Irinotecan significantly increased amounts of topoisomerase I covalently bound to DNA in stomach, duodenum, colon and liver. Concomitantly, the Irinotecan-treated group exihibited significantly higher amounts of DNA strand breaks in colon mucosa cells compared to the control group [5].

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