Abstract
The kinetics of the metabolic demethylation of temazepam were examined. Oxidative cleavage of the 1-methyl C–H bonds is rate-determining in the 13 000 g supernatant of mouse liver homogenate, as shown by the primary deuterium isotope effect (3.6) for demethylation of 1-CD3-labelled temazepam. With a reduced supply of NADPH, reduction of the cytochrome P-450–substrate complex becomes rate-limiting. Decomposition of the 1-N-hydroxymethyl intermediate is fast enough not to influence the rate of demethylation.
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