Guanethidine N-oxidation in human liver microsomes

Publisher Website
Google Scholar
Abstract
The capacity of human liver microsomes to N-oxidize guanethidine from 25 subjects has been assessed. Guanethidine N-oxidation was optimal at pH 8ṁ5 and proceeded at only 16% of the maximal rate at pH 7ṁ4. The mean rates of guanethidine N-oxidation at pH 8ṁ5 and 7ṁ4 were 2ṁ46 ± 0ṁ89 (mean ± s.d., n = 25) and 0ṁ38 ± 0ṁ22 (mean ± s.d., n = 22), respectively. Interindividual differences in the rate of guanethidine N-oxidation at pH 8ṁ5 and 7ṁ4 were 17- and 11-fold, respectively. The cytochrome P450 inhibitors, proadifen and 2,4-dichloro-6-phenylphenoxyethylamine (DPEA), at both pH 8ṁ5 and 7ṁ4 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.