PT  - JOURNAL ARTICLE
AU  - Moody, Joanna D.
AU  - Freeman, James P.
AU  - Cerniglia, Carl E.
TI  - Biotransformation of Doxepin by <em>Cunninghamella elegans</em>
DP  - 1999 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1157--1164
VI  - 27
IP  - 10
4099  - http://dmd.aspetjournals.org/content/27/10/1157.short
4100  - http://dmd.aspetjournals.org/content/27/10/1157.full
SO  - Drug Metab Dispos1999 Oct 01; 27
AB  - A filamentous fungus, Cunninghamella elegans ATCC 9245, was used as a microbial model of mammalian metabolism to biotransform doxepin, a tricyclic antidepressant drug. Doxepin is produced as an 85:15% mixture of the trans- (E) and cis- (Z) forms. After 96 h of incubation in Sabouraud dextrose broth, 28% of the drug was metabolized to 16 metabolites. No change in thetrans- (E) and cis- (Z) ratio of doxepin was observed. Metabolites were isolated by reversed phase HPLC and identified by 1H NMR and mass spectroscopic analysis. The major metabolites were (E)-2-hydroxydoxepin, (E)-3-hydroxydoxepin, (Z)-8-hydroxydoxepin, (E)-2-hydroxy-N-desmethyldoxepin, (E)-3-hydroxy-N-desmethyldoxepin, (E)-4-hydroxy-N-desmethyldoxepin, (Z)- and (E)-8-hydroxy-N-desmethyldoxepin, (E)-N-acetyl-N-desmethyldoxepin, (E)-N-desmethyl-N-formyldoxepin, (E)-N-acetyldidesmethyldoxepin, (E)-and (Z)-doxepin-N-oxide, and (E)- and (Z)-N-desmethyldoxepin. Six of the metabolites produced by C. elegans were essentially similar to those obtained in human metabolism studies, although nine novel metabolites were identified. U.S. Government