Cimetidine inhibits the in vitro N-demethylation of methadone

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.