N. Feifel et al., ROLE OF CYTOCHROME-P4502D6 IN THE METABOLISM OF BROFAROMINE - A NEW SELECTIVE MAO-A INHIBITOR, European Journal of Clinical Pharmacology, 45(3), 1993, pp. 265-269
The metabolic fate of brofaromine (CGP 11 305 A), a new, reversible, s
elective MAO-A inhibitor, has been assessed in poor (PM) and extensive
(EM) metabolizers of debrisoquine. Compared to EM, PM had significant
ly longer t1/2 (136 %) and larger AUC(0-infinity) (110 %) of the paren
t compound brofaromine and a lower C(max) (69 %) and AUC (0-72 h) (40
%) of its O-desmethyl metabolite. The mean metabolite/substrate ratio
(based on urine excretion) was about 6-times greater in EM than in PM.
Treatment with quinidine converted all EM into phenocopies of PM. All
pharmacokinetic parameters of brofaromine and O-desmethylbrofaromine
in EM treated with quinidine were similar to those of untreated PM, in
cluding the metabolite/substrate ratio. Quinidine treatment of PM did
not alter the pharmacokinetics of brofaromine or of its metabolite, no
r the metabolite/substrate ratio. The results indicate a role for the
debrisoquine type of oxidation polymorphism in the O-demethylation and
pharmacokinetics of brofaromine.