Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-19977

Koller-Lucae, S K; Suter, M J; Rentsch, K M; Schott, H; Schwendener, R (1999). Metabolism of the new liposomal anticancer drug N4-octadecyl-1-beta-D-arabinofuranosylcytosine in mice. Drug Metabolism and Disposition, 27(3):342-350.

[img]
Preview
PDF
1MB

Abstract

Metabolism and excretion of the new antitumor drug N4-octadecyl-1-beta-D-arabinofuranosylcytosine (NOAC) was investigated in mice. Mice were injected i.v. with tritium-labeled liposomal NOAC (4 micromol/mouse). Analysis of HPLC-purified extracts of liver homogenates by liquid chromatography coupled with mass spectrometry revealed only the presence of unmetabolized drug. To study the excretion of the administered drug, mice were injected with tritium-labeled liposomal NOAC or as comparison with 1-beta-D-arabinofuranosylcytosine (ara-C; 4 micromol/mouse) and housed up to 48 h in metabolic cages. Urine and feces were collected at different time points and the kinetics of excreted radioactivity were determined. After 48 h, 39% of the injected [5-3H]NOAC radioactivity was excreted in urine and 16% in feces, whereas ara-C radioactivity was only found in urine with 48% of the injected dose. Feces extracts and urine were purified by HPLC and radioactive fractions were further analyzed by liquid chromatography coupled with mass spectrometry. The radioactivity of feces extracts of NOAC-treated mice was composed of unmetabolized NOAC, hydroxylated NOAC (NOAC + OH), its sulfated derivative (NOAC + OSO3H), and unidentified metabolites, whereas in urine, the hydrophilic molecules ara-C and ara-U were found. During the period of 48 h only 2% of the injected NOAC was eliminated in its unmetabolized form, whereas 25% was identified as main metabolite ara-C. Urine collected during 48 h in ara-C-treated mice contained 33% of the injected dose as unmetabolized drug and 13% as the main metabolite ara-U. Thus, NOAC is metabolized by two major pathways, one leading to the hydrophilic metabolites ara-C and ara-U and the other to hydroxylated and sulfated NOAC.

Citations

16 citations in Web of Science®
14 citations in Scopus®
Google Scholar™

Downloads

12 downloads since deposited on 29 Jul 2009
56 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
DDC:570 Life sciences; biology
Language:English
Date:1999
Deposited On:29 Jul 2009 13:34
Last Modified:27 Nov 2013 18:05
Publisher:American Society for Pharmacology and Experimental Therapeutics
ISSN:0090-9556
Additional Information:Drug Metabolism and Disposition free text article
Official URL:http://dmd.aspetjournals.org/cgi/content/full/27/3/342
PubMed ID:10064564

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page