This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sun, L.
Right arrow Articles by Zhong, D.-F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, L.
Right arrow Articles by Zhong, D.-F.
Agricola
Right arrow Articles by Sun, L.
Right arrow Articles by Zhong, D.-F.

 Previous Article  |  Next Article 

Applied and Environmental Microbiology, May 2004, p. 2722-2727, Vol. 70, No. 5
0099-2240/04/$08.00+0     DOI: 10.1128/AEM.70.5.2722-2727.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Transformation of Verapamil by Cunninghamella blakesleeana

Lu Sun,1 Hai-Hua Huang,2 Lei Liu,2 and Da-Fang Zhong1*

Laboratory of Drug Metabolism and Pharmacokinetics,1 Department of Microbiology, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China2

Received 29 October 2003/ Accepted 26 February 2004

A filamentous fungus, Cunninghamella blakesleeana AS 3.153, was used as a microbial model of mammalian metabolism to transform verapamil, a calcium channel antagonist. The metabolites of verapamil were separated and assayed by the liquid chromatography-ion trap mass spectrometry method. After 96 h of incubation, nearly 93% of the original drug was metabolized to 23 metabolites. Five major metabolites were isolated by semipreparative high-performance liquid chromatography and were identified by proton nuclear magnetic resonance and electrospray mass spectrometry. Other metabolites were characterized according to their chromatographic behavior and mass spectral data. The major metabolic pathways of verapamil transformation by the fungus were N dealkylation, O demethylation, and sulfate conjugation. The phase I metabolites of verapamil (introduction of a functional group) by C. blakesleeana paralleled those in mammals; therefore, C. blakesleeana could be a useful tool for generating the mammalian phase I metabolites of verapamil.

* Corresponding author. Mailing address: Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China. Phone and fax: 86-24-23902539. E-mail: zhongdf{at}china.com.

Applied and Environmental Microbiology, May 2004, p. 2722-2727, Vol. 70, No. 5
0099-2240/04/$08.00+0     DOI: 10.1128/AEM.70.5.2722-2727.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»