Variable metabolism of pinacidil: lack of correlation with the debrisoquine and trimethylamine C- and N-oxidative polymorphisms.
1. The urinary excretion of pinacidil and its N-oxide in man was found to vary over a five-fold range. 2. Studies in individuals with inherited deficiencies for C-hydroxylation (debrisoquine type) and trimethylamine N-oxidation showed that the N-oxidation of pinacidil did not co-segregate with these oxidative polymorphisms. 3. It is concluded that the variable N-oxidation of pinacidil is most likely to be due to variations in the activity of the P-450 isozymes rather than in the microsomal flavoprotein containing mixed-function amine oxidase of Ziegler which is considered to be responsible for the N-oxidation of trimethylamine.
Ayesh
R
R
Department of Pharmacology, St Mary's Hospital Medical School, London.
Al-Waiz
M
M
McBurney
A
A
Mitchell
S C
SC
Idle
J R
JR
Ward
J W
JW
Smith
R L
RL
D000328:Adult; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D006146:Guanidines / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D008297:Male; D008744:Methylamines / Q000378:metabolism*; D008875:Middle Aged; D010084:Oxidation-Reduction; D010641:Phenotype; D020110:Pinacidil / Q000031:analogs & derivatives; D014665:Vasodilator Agents / Q000378:metabolism* / Q000652:urine
D006146:Guanidines; D007546:Isoquinolines; D008744:Methylamines; D014665:Vasodilator Agents; D020110:Pinacidil; C044893:pinacidil pyridine N-oxide; C023336:trimethylamine; D003647:Debrisoquin