[Relationship between amitriptyline metabolism and polymorphic debrisoquine hydroxylation in native Chinese volunteers].
The demethylation and hydroxylation of amitriptyline were calculated from the ratios between the area under concentration--time curve (AUC) of amitriptyline and its three metabolites in eight healthy Chinese volunteers after a single oral dose of 100 mg amitriptyline. Great interindividual differences in AUCs of amitriptyline and its metabolites were observed. HPLC method was used to determine the debrisoquine hydroxylation phenotype in seven out of the eight volunteers. Six subjects were found to be rapid and one slow debrisoquine hydroxylators. The ratio between debrisoquine and 4-hydroxydebrisoquine in urine correlated significantly with the rate of amitriptyline hydroxylation and the AUCs of amitriptyline and 10-hydroxyamitriptyline, but not with that of amitriptyline demethylation. There also was a weak correlation between total plasma clearance and the hydroxylation of debrisoquine. These data suggest that the hydroxylation of amitriptyline and debrisoquine may be regulated by similar enzymatic processes and the demethylation and hydroxylation processes in amitriptyline metabolism appear to undergo two separate pathways.
Zhang
X H
XH
Department of Psychiatry, Shanghai Medical University.
Yu
P
P
Gu
N F
NF
Yin
J L
JL
Jiang
W D
WD
D000328:Adult; D000639:Amitriptyline / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D044466:Asian People; D003647:Debrisoquin / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics; D009661:Nortriptyline / Q000031:analogs & derivatives / Q000097:blood; D010641:Phenotype; D011110:Polymorphism, Genetic; D013045:Species Specificity
C013567:10-hydroxynortriptyline; D000639:Amitriptyline; D009661:Nortriptyline; C033738:10-hydroxyamitriptyline; D003647:Debrisoquin