Feifel N, Kucher K, Fuchs L, Jedrychowski M, Schmidt E, Antonin K H, Bieck P R, Gleiter C H
Human Pharmacology Institute, Ciba-Geigy GmbH, Tübingen, Germany.
Eur J Clin Pharmacol. 1993;45(3):265-9. doi: 10.1007/BF00315394.
The metabolic fate of brofaromine (CGP 11 305 A), a new, reversible, selective MAO-A inhibitor, has been assessed in poor (PM) and extensive (EM) metabolizers of debrisoquine. Compared to EM, PM had significantly longer t1/2 (136%) and larger AUC(0-infinity) (110%) of the parent compound brofaromine and a lower Cmax (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-desmethyl-brofaromine in EM treated with quinidine were similar to those of untreated PM, including the metabolite/substrate ratio. Quinidine treatment of PM did not alter the pharmacokinetics of brofaromine or of its metabolite, nor the metabolite/substrate ratio. The results indicate a role for the debrisoquine type of oxidation polymorphism in the O-demethylation and pharmacokinetics of brofaromine.
已在异喹胍的慢代谢者（PM）和快代谢者（EM）中评估了新型可逆性选择性单胺氧化酶A抑制剂溴法罗明（CGP 11 305 A）的代谢命运。与EM相比，PM中母体化合物溴法罗明的t1/2显著延长（136%），AUC(0-∞)增大（110%），而其O-去甲基代谢产物的Cmax较低（69%），AUC(0-72 h)较低（40%）。平均代谢产物/底物比（基于尿排泄）在EM中约为PM中的6倍。用奎尼丁治疗可使所有EM转变为PM的表型。在用奎尼丁治疗的EM中，溴法罗明和O-去甲基溴法罗明的所有药代动力学参数与未治疗的PM相似，包括代谢产物/底物比。用奎尼丁治疗PM不会改变溴法罗明或其代谢产物的药代动力学，也不会改变代谢产物/底物比。结果表明，异喹胍型氧化多态性在溴法罗明的O-去甲基化和药代动力学中起作用。
