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The capacity of human liver microsomes to N-oxidize guanethidine from 25 subjects has been assessed. Guanethidine N-oxidation was optimal at pH 8.5 and proceeded at only 16% of the maximal rate at pH 7.4. The mean rates of guanethidine N-oxidation at pH 8.5 and 7.4 were 2.46 +/- 0.89 (mean +/- s.d., n = 25) and 0.38 +/- 0.22 (mean +/- s.d., n = 22), respectively. Interindividual differences in the rate of guanethidine N-oxidation at pH 8.5 and 7.4 were 17- and 11-fold, respectively. The cytochrome P450 inhibitors, proadifen and 2,4-dichloro-6-phenylphenoxyethylamine (DPEA), at both pH 8.5 and 7.4 caused less than 20% reduction in the rate of guanethidine N-oxidation by human liver microsomes. These data indicate that guanethidine N-oxidation can be used as a measure of flavin-containing monooxygenase activity in human liver.
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