RT Journal Article SR Electronic T1 Biotransformation of Mirtazapine by Cunninghamella Elegans JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1274 OP 1279 DO 10.1124/dmd.30.11.1274 VO 30 IS 11 A1 Joanna D. Moody A1 James P. Freeman A1 Peter P. Fu A1 Carl E. Cerniglia YR 2002 UL http://dmd.aspetjournals.org/content/30/11/1274.abstract 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