Tags

Type your tag names separated by a space and hit enter

Biotransformation of doxepin by Cunninghamella elegans.
Drug Metab Dispos. 1999 Oct; 27(10):1157-64.DM

Abstract

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 the trans- (E) and cis- (Z) ratio of doxepin was observed. Metabolites were isolated by reversed phase HPLC and identified by (1)H 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.

Authors+Show Affiliations

Division of Microbiology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079-7341, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10497142

Citation

Moody, J D., et al. "Biotransformation of Doxepin By Cunninghamella Elegans." Drug Metabolism and Disposition: the Biological Fate of Chemicals, vol. 27, no. 10, 1999, pp. 1157-64.
Moody JD, Freeman JP, Cerniglia CE. Biotransformation of doxepin by Cunninghamella elegans. Drug Metab Dispos. 1999;27(10):1157-64.
Moody, J. D., Freeman, J. P., & Cerniglia, C. E. (1999). Biotransformation of doxepin by Cunninghamella elegans. Drug Metabolism and Disposition: the Biological Fate of Chemicals, 27(10), 1157-64.
Moody JD, Freeman JP, Cerniglia CE. Biotransformation of Doxepin By Cunninghamella Elegans. Drug Metab Dispos. 1999;27(10):1157-64. PubMed PMID: 10497142.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biotransformation of doxepin by Cunninghamella elegans. AU - Moody,J D, AU - Freeman,J P, AU - Cerniglia,C E, PY - 1999/9/25/pubmed PY - 1999/9/25/medline PY - 1999/9/25/entrez SP - 1157 EP - 64 JF - Drug metabolism and disposition: the biological fate of chemicals JO - Drug Metab. Dispos. VL - 27 IS - 10 N2 - 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 the trans- (E) and cis- (Z) ratio of doxepin was observed. Metabolites were isolated by reversed phase HPLC and identified by (1)H 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. SN - 0090-9556 UR - https://www.unboundmedicine.com/medline/citation/10497142/Biotransformation_of_doxepin_by_Cunninghamella_elegans_ L2 - http://dmd.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10497142 DB - PRIME DP - Unbound Medicine ER -