PT  - JOURNAL ARTICLE
AU  - Moody, Joanna D.
AU  - Freeman, James P.
AU  - Fu, Peter P.
AU  - Cerniglia, Carl E.
TI  - Biotransformation of Mirtazapine by <em>Cunninghamella Elegans</em>
AID  - 10.1124/dmd.30.11.1274
DP  - 2002 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 1274--1279
VI  - 30
IP  - 11
4099  - http://dmd.aspetjournals.org/content/30/11/1274.short
4100  - http://dmd.aspetjournals.org/content/30/11/1274.full
SO  - Drug Metab Dispos2002 Nov 01; 30
AB  - The fungus Cunninghamella elegans was used as a microbial model of mammalian metabolism to biotransform the tetracyclic antidepressant drug mirtazapine, which is manufactured as a racemic mixture of R(−)- and S(+)-enantiomers. In 168 h, C. elegans transformed 91% of the drug into the following seven metabolites: 8-hydroxymirtazapine,N-desmethyl-8-hydroxymirtazapine,N-desmethylmirtazapine, 13-hydroxymirtazapine, mirtazapine N-oxide, 12-hydroxymirtazapine, andN-desmethyl-13-hydroxymirtazapine. Circular dichroism spectral analysis of unused mirtazapine indicated that it was slightly enriched with the R(−)-enantiomer. When the fungus was treated with the optically pure forms of the drug, theS(+)-enantiomer produced all seven metabolites whereas the R(−)-enantiomer produced only 8-hydroxymirtazapine,N-desmethyl-8-hydroxymirtazapine,N-desmethylmirtazapine, and mirtazapineN-oxide. C. elegans produced five mammalian and two novel metabolites and is therefore a suitable microbial model for mirtazapine metabolism. U.S. Government