O-demethylation of dextromethorphan using microbial cultures.
The potential of various microbes to metabolize the dextromethorphan (DXM) , a CYP 2D6 substrate was studied to investigate similarities between microbial and mammalian metabolism. Eight microbes were screened for their ability to metabolize DXM in a manner comparable to humans with a view to develop alternative systems to study human drug metabolism. The major metabolite of DXM produced by Saccharomyces cerevisiae (NCIM 3090) was characterized by HPLC and Liquid Chromatography Mass Spectrometry (LC/MS). DXM was biotransformed by Saccharomyces cerevisiae into a major metabolite dextrorphan which is a known , active metabolite of DXM in human. The microbial metabolism of DXM was similar to the metabolism in mammals. The Saccharomyces cerevisiae could be used as a suitable model strain in vitro to mimic CYP 2D6 metabolism and to produce dextrorphan an active metabolite of DXM for further pharmacological, toxicological studies.
School of Pharmaceutical Sciences, Sri Padmavathi Mahila VisvaVidyalayam, Tirupati - 517 502, A.P., India.
Samathoti
S
Prasanthi
Maravajhala
M
Vidyavathi
Koganti V S R G
KV
Prasad
Devarakonda Rama
DR
Krishna
D000996:Antitussive Agents / Q000493:pharmacokinetics*; D001419:Bacteria / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D003640:Dealkylation; D003915:Dextromethorphan / Q000493:pharmacokinetics*; D003917:Dextrorphan / Q000378:metabolism; D005658:Fungi / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D000996:Antitussive Agents; D003917:Dextrorphan; D003915:Dextromethorphan; D019389:Cytochrome P-450 CYP2D6