Cimetidine inhibits the in vitro N-demethylation of methadone
Dawson, G.W.; Vestal, R.E.
Research Communications in Chemical Pathology and Pharmacology 46(2): 301-304
1984
ISSN/ISBN: 0034-5164 PMID: 6515123 Document Number: 223482
The effect of cimetidine on the metabolism of methadone was investigated in hepatic microsomes isolated from male Sprague-Dawley rats. N-demethylation of methadone was determined by formation of formaldehyde. Cimetidine inhibited methadone N-demethylation in a noncompetitive manner with an IC50 of 5.3 X 10(-4) M. This observation is consistent with previous reports of microsomal enzyme inhibition by cimetidine and suggests that caution must be exercised when methadone and cimetidine are co-administered to patients in order to avoid excessive sedation or respiratory depression.