Role of cytochrome P4502D6 in the metabolism of brofaromine. A new selective MAO-A inhibitor
| Autor: | P. R. Bieck, E. K. Schmidt, C. H. Gleiter, M. Jedrychowski, K. Kucher, N. Feifel, L. Fuchs, K. H. Antonin |
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| Rok vydání: | 1993 |
| Předmět: |
Quinidine
Adult Male Monoamine Oxidase Inhibitors Metabolite Cmax Pharmacology 030226 pharmacology & pharmacy Mixed Function Oxygenases Excretion 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Cytochrome P-450 Enzyme System Piperidines Brofaromine medicine Cytochrome P-450 Enzyme Inhibitors Humans Pharmacology (medical) General Medicine 3. Good health Phenotype Debrisoquine chemistry Cytochrome P-450 CYP2D6 Female 030217 neurology & neurosurgery Drug metabolism medicine.drug |
| Zdroj: | European journal of clinical pharmacology. 45(3) |
| ISSN: | 0031-6970 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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